text:
Associate Professor SSD ING-IND 25 (DIFARMA)
aabarba@unisa.it
Unisa personal page
Dr. Anna Angela Barba got her Laurea in Chemical Engineering, summa cum laude, in May 1997, then she gained the Ph.D. degree in Chemical Engineering in 2002. Starting from 1999 she had a CNR fellowship (one year), a post-doctoral grant (2002-2004) and worked at some research projects as external consultant at the Department of Chemical and Food Engineering, faculty of Engineering, University of Salerno.
In February 2005 she obtained a position as assistant professor in Chemical Plants at the Department of Pharmaceutical Sciences, Faculty of Pharmacy, which she joined in October 2005.
She had, since a.y. 2005/2006, the cathedra of Pharmaceutical Industrial Plants. She also had and has didactic activity in post-degree corse. She is a member of the faculty board of the doctorate of research in Chemical Engineering.
The research activities of dr. Barba, developed mainly at the University of Salerno, are developed in the field of power applications of electromagnetic field to the development of innovative methodologies and equipments for microwave assisted heating. From October 2002 to March 2003 she worked as post-doc research fellow at the Technical University of Eindhoven, TUE (NL) – Department of Electrical Engineering / Department of Chemical Engineering and Chemistry – where was involved in research activities on pulsed plasma.
Recently, dr. Barba addressed her research activities to the transfer of Chemical Engineering processes and methods to pharmaceutical productions. Her activities, developed in different scientific collaborations and characterized by experimental and modeling actions, are based on the use of electromagnetic energy (microwaves region) in heating intensified processes (cooking, drying, blanching, curing) of vegetal matrices and pharmaceutical ingredients. Non-conventional analytic procedures are also developed to study the dielectric behavior of materials (nanometallic powders, composite, biopolymeric hydrogels).
Dr. Anna Angela Barba was scientific responsible of research projects funded bybudget Ateneo and she was involved and is currently involved in different financed projects.
She is co-authors of many publications: papers on international and national journals, communications to international and national conferences, chapters in books/monographs.
Alginate Biodistribution Biopolymer Chelating Agents Controlled drug release dielectric properties drug delivery Drug Delivery Systems drug release Erosion Granulation HPMC Hydrogel Characterization Hydrogel Modeling Hydrogels In silico In vitro liposome Mathematical modeling Micro and Nano Vectors microencapsulation microwave heating Modeling Pharmacokinetics siRNA Tecnagri Texture analysis Theophylline ultrasonic atomization Wet granulation
All years 20202019201820172016201520142013201220112010200920082007200620052004200320022001200019990000 All types Journal ArticlesBook ChaptersIncollectionsInproceedings
160 entries « ‹ 1 of 4 › »
De Piano, Raffaella ; Caccavo, Diego; Cascone, Sara; Festa, Caterina; Lamberti, Gaetano; Barba, Anna Angela
Drug release from hydrogel-based matrix systems partially coated: experiments and modeling Journal Article
Journal of Drug Delivery Science and Technology, 2020.
Abstract | Links | BibTeX | Tags: drug release, Modeling, Tablets, Theophylline
@article{Piano}2020,
title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},
author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dihub},
doi = {10.1016/j.jddst.2020.102146},
abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},
keywords = {drug release, Modeling, Tablets, Theophylline},
Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.
https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dih[...]
doi:10.1016/j.jddst.2020.102146
De Simone, Veronica ; Dalmoro, Annalisa; Bochicchio, Sabrina; Caccavo, Diego; Lamberti, Gaetano; Bertoncin, Paolo; Barba, Anna Angela
Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems Journal Article
Journal of Drug Delivery Science and Technology, 59 , pp. 7, 2020.
Abstract | Links | BibTeX | Tags: Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation
@article{Simone}2020b,
title = {Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems},
author = {Veronica {De Simone} and Annalisa Dalmoro and Sabrina Bochicchio and Diego Caccavo and Gaetano Lamberti and Paolo Bertoncin and Anna Angela Barba},
abstract = {Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers).},
keywords = {Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation},
Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers).
Milocco, Alessio; Scuor, Nicola; Lughi, Vanni; Lamberti, Gaetano; Barba, Anna Angela; Divittorio, Rosario; Grassi, Gabriele; Perkan, Andrea; Grassi, Mario; Abrami, Michela
Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty Journal Article
Journal of Applied Polymer Science, 137 (25), pp. 10, 2020.
Abstract | Links | BibTeX | Tags: alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis
@article{Milocco2020,
title = {Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty },
author = {Alessio Milocco and Nicola Scuor and Vanni Lughi and Gaetano Lamberti and Anna Angela Barba and Rosario Divittorio and Gabriele Grassi and Andrea Perkan and Mario Grassi and Michela Abrami},
url = {https://onlinelibrary.wiley.com/doi/epdf/10.1002/app.48539},
doi = {10.1002/app.48539},
journal = {Journal of Applied Polymer Science},
pages = {10},
abstract = {To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. },
keywords = {alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis},
To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter.
https://onlinelibrary.wiley.com/doi/epdf/10.1002/app.48539
doi:10.1002/app.48539
Barba, Anna Angela; Naddeo, Carlo; Caputo, Silvestro; Lamberti, Gaetano; D'Amore, Matteo; Dalmoro, Annalisa
Microwave Treatments of Cereals: Effects on Thermophysical and Parenchymal-Related Properties Journal Article
Foods, 9 (6), pp. 14, 2020.
Abstract | Links | BibTeX | Tags: cereals; dielectric properties, food sanitization, microwave heating, pest disinfestation, thermal properties
@article{Barba2020b,
title = {Microwave Treatments of Cereals: Effects on Thermophysical and Parenchymal-Related Properties},
author = {Anna Angela Barba and Carlo Naddeo and Silvestro Caputo and Gaetano Lamberti and Matteo D'Amore and Annalisa Dalmoro},
url = {https://www.mdpi.com/2304-8158/9/6/711},
doi = {10.3390/foods9060711 },
journal = {Foods},
abstract = {Dielectric heating is one of the most interesting techniques for pest disinfestation. However, most of the literature works give information about the ability of microwave treatments at different power-time conditions to kill insects; less is given about the analysis of matrices structural properties and heat transport. Accordingly, the aim of this work is to investigate the effect of microwave treatments, applied for pest disinfestation, on heat transport behavior and physical/structural properties, such as water uptake capability, mineral losses, texture change, and germination capability, of most consumed cereals in human diet, such as weak wheat, durum wheat, and corn. Two different radiative treatments were performed: one in time-temperature conditions capable of inactivating the weed fauna, and the other at high temperatures of ~150 °C, simulating uncontrolled treatments. Heat transport properties were measured and showed to keep unvaried during both effective and uncontrolled microwave treatments. Instead, grain physical properties were worsened when exposed to high temperatures (reduction of germination ability and texture degradation). The achieved results, on the one hand, provide new structural and heat transport data of cereals after microwave treatments, actually not present in the literature, and on the other, they confirm the importance of correctly performing microwave treatments for an effective disinfestation without affecting matrices physical properties and nutritional features.},
keywords = {cereals; dielectric properties, food sanitization, microwave heating, pest disinfestation, thermal properties},
Dielectric heating is one of the most interesting techniques for pest disinfestation. However, most of the literature works give information about the ability of microwave treatments at different power-time conditions to kill insects; less is given about the analysis of matrices structural properties and heat transport. Accordingly, the aim of this work is to investigate the effect of microwave treatments, applied for pest disinfestation, on heat transport behavior and physical/structural properties, such as water uptake capability, mineral losses, texture change, and germination capability, of most consumed cereals in human diet, such as weak wheat, durum wheat, and corn. Two different radiative treatments were performed: one in time-temperature conditions capable of inactivating the weed fauna, and the other at high temperatures of ~150 °C, simulating uncontrolled treatments. Heat transport properties were measured and showed to keep unvaried during both effective and uncontrolled microwave treatments. Instead, grain physical properties were worsened when exposed to high temperatures (reduction of germination ability and texture degradation). The achieved results, on the one hand, provide new structural and heat transport data of cereals after microwave treatments, actually not present in the literature, and on the other, they confirm the importance of correctly performing microwave treatments for an effective disinfestation without affecting matrices physical properties and nutritional features.
https://www.mdpi.com/2304-8158/9/6/711
doi:10.3390/foods9060711
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela
Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling Journal Article
European Journal of Pharmaceutics and Biopharmaceutics, 152 , pp. 299-306, 2020.
Abstract | Links | BibTeX | Tags: Agarose, drug delivery, Hydrogels, Modeling, Poroviscoelasticity
@article{Caccavo2020,
title = {Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling},
author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba},
url = {https://doi.org/10.1016/j.ejpb.2020.05.020},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
abstract = {Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a "poroviscoelastic" behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient.},
keywords = {Agarose, drug delivery, Hydrogels, Modeling, Poroviscoelasticity},
Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a "poroviscoelastic" behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient.
https://doi.org/10.1016/j.ejpb.2020.05.020
Bochicchio, Sabrina; Dalmoro, Annalisa; Lamberti, Gaetano; Barba, Anna Angela
Advances in Nanoliposomes Production for Ferrous Sulfate Delivery Journal Article
Pharmaceutics, 12 (5), pp. 445, 2020.
Abstract | Links | BibTeX | Tags: drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication
@article{Bochicchio2020b,
title = {Advances in Nanoliposomes Production for Ferrous Sulfate Delivery},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba},
editor = {MDPI},
url = {https://www.mdpi.com/1999-4923/12/5/445/pdf},
doi = {10.3390/pharmaceutics12050445},
journal = {Pharmaceutics},
pages = {445},
abstract = {In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization. },
keywords = {drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication},
In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization.
https://www.mdpi.com/1999-4923/12/5/445/pdf
doi:10.3390/pharmaceutics12050445
Bochicchio, Sabrina; Dalmoro, Annalisa; Simone, Veronica De; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela
Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems Journal Article
Cosmetics, 7 (22), pp. 13, 2020.
Abstract | Links | BibTeX | Tags: antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery
@article{Bochicchio2020,
title = {Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Veronica De Simone and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba},
url = {https://www.mdpi.com/2079-9284/7/2/22/pdf},
doi = {10.3390/cosmetics7020022},
journal = {Cosmetics},
abstract = {Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84\textendash145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. },
keywords = {antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery},
Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84–145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field.
https://www.mdpi.com/2079-9284/7/2/22/pdf
doi:10.3390/cosmetics7020022
Barba, Anna Angela; Dalmoro, Annalisa; Bochicchio, Sabrina; Simone, Veronica De; Caccavo, Diego; Iannone, Marco; Lamberti, Gaetano
Engineering approaches for drug delivery systems production and characterization Journal Article
International Journal of Pharmaceutics, 2020.
Abstract | Links | BibTeX | Tags: drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors
@article{Barba2020,
title = {Engineering approaches for drug delivery systems production and characterization},
author = {Anna Angela Barba and Annalisa Dalmoro and Sabrina Bochicchio and Veronica De Simone and Diego Caccavo and Marco Iannone and Gaetano Lamberti},
url = {https://www.sciencedirect.com/science/article/pii/S0378517320302519},
doi = {10.1016/j.ijpharm.2020.119267},
abstract = {To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs).
In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.},
keywords = {drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors},
To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs).
In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.
doi:10.1016/j.ijpharm.2020.119267
Lamberti, Gaetano; Barba, Anna Angela
Drug Delivery of siRNA Therapeutics Journal Article
Pharmaceutics, 12(2) (178), 2020.
Links | BibTeX | Tags: aptamers, Drug Delivery Systems, gene therapy, liposomes, nanoparticles, polycations, siRNA
title = {Drug Delivery of siRNA Therapeutics},
author = {Gaetano Lamberti and Anna Angela Barba},
volume = {12(2)},
keywords = {aptamers, Drug Delivery Systems, gene therapy, liposomes, nanoparticles, polycations, siRNA},
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano
Polymeric and lipid-based systems for controlled drug release: an engineering point of view Book Chapter
Grumezescu, Alexandru Mihai (Ed.): Chapter 10, pp. 267-304, Elsevier, 2019, ISBN: 978-0-12-816505-8.
Abstract | Links | BibTeX | Tags: characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes
@inbook{Barba2019c,
title = {Polymeric and lipid-based systems for controlled drug release: an engineering point of view},
author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Diego Caccavo and Sara Cascone and Gaetano Lamberti},
editor = {Alexandru Mihai Grumezescu},
url = {https://www.sciencedirect.com/science/article/pii/B9780128165058000138?via%3Dihub#kys0010},
doi = {10.1016/B978-0-12-816505-8.00013-8},
isbn = {978-0-12-816505-8},
chapter = {10},
abstract = {Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view.
The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems' preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared.},
keywords = {characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes},
tppubtype = {inbook}
Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view.
The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems' preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared.
https://www.sciencedirect.com/science/article/pii/B9780128165058000138?via%3Dihu[...]
doi:10.1016/B978-0-12-816505-8.00013-8
Barba, Anna Angela; Bochicchio, Sabrina; Bertoncin, Paolo; Lamberti, Gaetano; Dalmoro, Annalisa
Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches Journal Article
Coatings, 9 (491), pp. 1-15, 2019.
Abstract | Links | BibTeX | Tags: Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique
title = {Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches },
author = {Anna Angela Barba and Sabrina Bochicchio and Paolo Bertoncin and Gaetano Lamberti and Annalisa Dalmoro},
url = {https://www.mdpi.com/2079-6412/9/8/491/htm},
doi = {10.3390/coatings9080491},
journal = {Coatings},
abstract = {Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability.},
keywords = {Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique},
Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability.
https://www.mdpi.com/2079-6412/9/8/491/htm
doi:10.3390/coatings9080491
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Lamberti, Gaetano
Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications Journal Article
Pharmaceutics, 11 (360), 2019.
Abstract | Links | BibTeX | Tags: clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA
title = {Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications},
author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti},
url = {https://www.mdpi.com/1999-4923/11/8/360},
abstract = {In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming "the latest generation medicine" with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs},
keywords = {clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA},
In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming "the latest generation medicine" with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs
Dalmoro, Annalisa; Bochicchio, Sabrina; Lamberti, Gaetano; Bertoncin, Paolo; Janssens, Barbara; Barba, Anna Angela
Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology Journal Article
RSC Advances, 9 , pp. 19800-19812, 2019.
Abstract | Links | BibTeX | Tags: Drug Delivery Systems, Micro and Nano Vectors
@article{Dalmoro2019,
title = {Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology },
author = {Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Paolo Bertoncin and Barbara Janssens and Anna Angela Barba},
url = {https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k},
doi = {10.1039/C9RA03022K},
journal = {RSC Advances},
pages = {19800-19812},
abstract = {Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer\textendashlipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.},
keywords = {Drug Delivery Systems, Micro and Nano Vectors},
Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer–lipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.
https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k
doi:10.1039/C9RA03022K
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela
Effect of binder and load solubility properties on HPMC granules produced by wet granulation process Journal Article
Journal of Drug Delivery Science and Technology, 49 , pp. 513-520, 2019.
Abstract | Links | BibTeX | Tags: Granulation, HPMC
@article{Simone}2019,
title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba},
abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.},
keywords = {Granulation, HPMC},
Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.
De Simone, Veronica ; Caccavo, Diego; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Wet-granulation process: phenomenological analysis and process parameters optimization Journal Article
Powder Technology, 340 , pp. 411-419, 2018.
title = {Wet-granulation process: phenomenological analysis and process parameters optimization},
author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
doi = {10.1016/j.powtec.2018.09.053},
journal = {Powder Technology},
abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.},
Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000–10,000 μm) as the main variable of interest.
doi:10.1016/j.powtec.2018.09.053
De Simone, Veronica ; Caccavo, Diego; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters Book Chapter
Kyzas, George (Ed.): Chapter 5, IntechOpen, 2018, ISBN: 978-1-78984-308-8.
Abstract | Links | BibTeX | Tags: Granulation, HPMC, Mathematical modeling
@inbook{Simone}2018c,
title = {Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters},
author = {Veronica {De Simone} and Diego Caccavo and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
editor = {George Kyzas},
url = {https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters},
doi = {10.5772/intechopen.79840},
publisher = {IntechOpen},
chapter = {5},
abstract = {Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.},
keywords = {Granulation, HPMC, Mathematical modeling},
Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.
https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phe[...]
doi:10.5772/intechopen.79840
Bochicchio, Sabrina; Dalmoro, Annalisa; Bertoncin, Paolo; Lamberti, Gaetano; Moustafine, Rouslan I; Barba, Anna Angela
Design and production of hybrid nanoparticles with polymeric-lipid shell–core structures: conventional and next-generation approaches Journal Article
RSC Advances, 8 , pp. 34614–34624, 2018.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
title = {Design and production of hybrid nanoparticles with polymeric-lipid shell\textendashcore structures: conventional and next-generation approaches},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Paolo Bertoncin and Gaetano Lamberti and Rouslan I. Moustafine and Anna Angela Barba },
url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract},
doi = {10.1039/c8ra07069e},
pages = {34614\textendash34624},
abstract = {Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite
their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids
as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for
liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the
natural biocompatible polymer chitosan to achieve stable shell\textendashcore nanostructures. Covered
nanoliposomes were produced using an innovative continuous method based on microfluidic principles.
The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties,
size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and
chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method
were compared with those of the conventional dropwise method and the obtained products. The
proposed simil-microfluidic method led to the production of stable and completely chitosan-covered
liposomes with a shell\textendashcore nanostructure that avoided the disadvantages inherent in the conventional
method (which are time-consuming and/or require bulky and more expensive equipment).},
keywords = {Micro and Nano Vectors},
Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite
natural biocompatible polymer chitosan to achieve stable shell–core nanostructures. Covered
liposomes with a shell–core nanostructure that avoided the disadvantages inherent in the conventional
method (which are time-consuming and/or require bulky and more expensive equipment).
https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract
doi:10.1039/c8ra07069e
Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems Journal Article
European Journal of Pharmaceutical Sciences, 121 , pp. 16-28, 2018.
@article{Dalmoro2018b,
title = {Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems},
author = {Annalisa Dalmoro and Sabrina Bochicchio and Shamil F. Nasibullin and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.
Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.
The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.
Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.},
Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.
Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.
Caccavo, Diego; Vietri, Antonella; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Modeling the mechanics and the transport phenomena in hydrogels Book Chapter
Manca, Davide (Ed.): Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Chapter 12, 2018.
Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling
@inbook{Caccavo2018b,
title = {Modeling the mechanics and the transport phenomena in hydrogels},
author = {Diego Caccavo and Antonella Vietri and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },
editor = {Davide Manca},
url = {https://www.sciencedirect.com/science/article/pii/B978044463964600012X},
doi = {10.1016/B978-0-444-63964-6.00012-X},
booktitle = {Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications},
abstract = {Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as\textemdashin principle\textemdashany other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).},
keywords = {Hydrogel Characterization, Hydrogel Modeling},
Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).
https://www.sciencedirect.com/science/article/pii/B978044463964600012X
doi:10.1016/B978-0-444-63964-6.00012-X
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour Journal Article
Chemical Society Reviews, 47 (7), pp. 2357-2373, 2018, ISSN: 0306-0012.
title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract},
doi = {10.1039/C7CS00638A},
journal = {Chemical Society Reviews},
pages = {2357-2373},
abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.},
Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure–property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.
http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract
doi:10.1039/C7CS00638A
Dalmoro, Annalisa; Naddeo, Carlo; Caputo, Silvestro; Lamberti, Gaetano; Guadagno, Liberata; D'Amore, Matteo; Barba, Anna Angela
On the relevance of thermophysic characterizations in microwave treatments of legumes Journal Article
Food & Function, 9 (3), pp. 1816-1828, 2018, ISSN: 2042-650X.
Abstract | Links | BibTeX | Tags: legumes, microwave, Tecnagri, thermophysic
title = {On the relevance of thermophysic characterizations in microwave treatments of legumes},
author = {Annalisa Dalmoro and Carlo Naddeo and Silvestro Caputo and Gaetano Lamberti and Liberata Guadagno and Matteo D'Amore and Anna Angela Barba},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C7FO01488K},
doi = {10.1039/C7FO01488K},
issn = {2042-650X},
journal = {Food & Function},
abstract = {This study is focused on the characterization of thermal behavior and physical properties of most consumed legumes in daily diet such as beans, lentils and chickpeas. Because of a lack of knowledge in literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable to inactivate the infesting fauna, and one simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenols composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also performed. Examined legumes thermal properties were found comparable for all samples. Similarly, no significative differences in antinutritional factors, polyphenols and tannins, content among all samples were detected. Under structural point of view, samples exposed to high temperatures have been shown a texture degradation and in turn, losses of mineral nutrient during soaking processes. Moreover, their germinative capability was drastically reduced. These latter results highlighted how is important to correctly perform radiative microwave process in order to both assure an effective and safe disinfestation and avoid nutritional values losses and physical properties worsening.},
keywords = {legumes, microwave, Tecnagri, thermophysic},
This study is focused on the characterization of thermal behavior and physical properties of most consumed legumes in daily diet such as beans, lentils and chickpeas. Because of a lack of knowledge in literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable to inactivate the infesting fauna, and one simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenols composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also performed. Examined legumes thermal properties were found comparable for all samples. Similarly, no significative differences in antinutritional factors, polyphenols and tannins, content among all samples were detected. Under structural point of view, samples exposed to high temperatures have been shown a texture degradation and in turn, losses of mineral nutrient during soaking processes. Moreover, their germinative capability was drastically reduced. These latter results highlighted how is important to correctly perform radiative microwave process in order to both assure an effective and safe disinfestation and avoid nutritional values losses and physical properties worsening.
http://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C7FO01488K
doi:10.1039/C7FO01488K
HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties Journal Article
Carbohydrate Polymers, 181 , pp. 939-947, 2018.
Abstract | Links | BibTeX | Tags: Granulation
@article{{DeSimone}2018,
title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba },
doi = {10.1016/j.carbpol.2017.11.056},
journal = {Carbohydrate Polymers},
abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.},
keywords = {Granulation},
Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.
doi:10.1016/j.carbpol.2017.11.056
Caccavo, Diego; Barba, Anna Angela; D'Amore, Matteo; De Piano, Raffaella ; Lamberti, Gaetano; Rossi, Alessandra; Colombo, Paolo
Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix® Journal Article
European Journal of Pharmaceutics and Biopharmaceutics, 121 , pp. 24-31, 2017, ISSN: 0939-6411.
@article{Caccavo2017b,
title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®},
author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo},
abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.},
The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.
Caccavo, Diego; Cascone, Sara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela
HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture Journal Article
Chemical Engineering Communications, 204 (12), pp. 1333-1340, 2017, ISSN: 0098-6445.
title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture},
author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398},
doi = {10.1080/00986445.2017.1362398 },
journal = {Chemical Engineering Communications},
abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.},
One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.
http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398
doi:10.1080/00986445.2017.1362398
Bochicchio, Sabrina; Sala, Marina; Spensiero, Antonia; Scala, Maria Carmina; Gomez-Monterrey, Isabel; Lamberti, Gaetano; Barba, Anna Angela
On the design of tailored liposomes for KRX29 peptide delivery Journal Article
New Journal of Chemistry, 41 (19), pp. 11280-11290, 2017, ISSN: 1144-0546.
Abstract | Links | BibTeX | Tags: liposome, peptide
title = {On the design of tailored liposomes for KRX29 peptide delivery },
author = {Sabrina Bochicchio and Marina Sala and Antonia Spensiero and Maria Carmina Scala and Isabel Gomez-Monterrey and Gaetano Lamberti and Anna Angela Barba },
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ03115G},
doi = { 10.1039/C7NJ03115G},
journal = {New Journal of Chemistry},
abstract = {The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 \textendash 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction.},
keywords = {liposome, peptide},
The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 – 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction.
http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ03115G
doi: 10.1039/C7NJ03115G
Bochicchio, Sabrina; Lamberti, Gaetano; Barba, Anna Angela
Phenomenological and Formulation Aspects in Tailored Nanoliposome Production Book Chapter
Liposomes, Chapter 2, IntechOpen, 2017.
Abstract | Links | BibTeX | Tags: cell‐mimetic system, gene therapy, liposome, nanoliposomes delivery systems, nutraceuticals, personalized carriers, simil‐microfluidic approach, ultrasonic size reduction
@inbook{Bochicchio2017d,
title = {Phenomenological and Formulation Aspects in Tailored Nanoliposome Production},
author = {Sabrina Bochicchio and Gaetano Lamberti and Anna Angela Barba},
url = {https://www.intechopen.com/books/liposomes/phenomenological-and-formulation-aspects-in-tailored-nanoliposome-production},
booktitle = {Liposomes},
abstract = {Liposomes as cell‐mimetic system have attracted wide attention of researchers in various branches of the drug delivery topic as they can be highly functionalized and personalized, thus solving the major drawbacks of bioactive molecules linked to their low stability, limited membrane permeability, short half‐life and low bioavailability. The development of sustainable processes able to produce ad hoc liposomes in a rapid manner through the use of not‐laboured techniques, avoiding drastic conditions, is of great relevance for the industrial sector. In this chapter, two novel liposome production processes, the ultrasound‐assisted thin‐film hydration and the simil‐microfluidic techniques sharing the same size reduction/homogenization preparative step, are presented. The phenomenological aspects involved in vectors constitution through the duty cycle sonication process (bilayer rupture/vesicles formation mechanisms) and through the simil‐microfluidic approach (intubated flows interdiffusion mechanisms) are described. Finally, two applications as case histories involving the use of the developed techniques for relevant classes of active molecule delivery are described. In particular, a pharmaceutical application concerns the encapsulation of short‐interfering RNA (siRNA) molecule, used for gene therapy, inside cationic nanoliposomes, and a nutraceutical application consists in the production of ferrous sulphate anionic liposomal formulations with improved features compared to those already present on the market.},
keywords = {cell‐mimetic system, gene therapy, liposome, nanoliposomes delivery systems, nutraceuticals, personalized carriers, simil‐microfluidic approach, ultrasonic size reduction},
Liposomes as cell‐mimetic system have attracted wide attention of researchers in various branches of the drug delivery topic as they can be highly functionalized and personalized, thus solving the major drawbacks of bioactive molecules linked to their low stability, limited membrane permeability, short half‐life and low bioavailability. The development of sustainable processes able to produce ad hoc liposomes in a rapid manner through the use of not‐laboured techniques, avoiding drastic conditions, is of great relevance for the industrial sector. In this chapter, two novel liposome production processes, the ultrasound‐assisted thin‐film hydration and the simil‐microfluidic techniques sharing the same size reduction/homogenization preparative step, are presented. The phenomenological aspects involved in vectors constitution through the duty cycle sonication process (bilayer rupture/vesicles formation mechanisms) and through the simil‐microfluidic approach (intubated flows interdiffusion mechanisms) are described. Finally, two applications as case histories involving the use of the developed techniques for relevant classes of active molecule delivery are described. In particular, a pharmaceutical application concerns the encapsulation of short‐interfering RNA (siRNA) molecule, used for gene therapy, inside cationic nanoliposomes, and a nutraceutical application consists in the production of ferrous sulphate anionic liposomal formulations with improved features compared to those already present on the market.
https://www.intechopen.com/books/liposomes/phenomenological-and-formulation-aspe[...]
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette
Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study Journal Article
International Journal of Pharmaceutics, 528 (1-2), pp. 705-713, 2017, ISSN: 0378-5173.
Abstract | Links | BibTeX | Tags: Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling
@article{Larsson2017,
title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study},
author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Susanna Abrahms\'{e}n-Alami and Anna Virid\'{e}n and Anette Larsson},
abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. },
keywords = {Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling},
The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.
Bochicchio, Sabrina; Dalmoro, Annalisa; Recupido, Federica; Lamberti, Gaetano; Barba, Anna Angela
Nanoliposomes Production by a Protocol Based on a Simil-Microfluidic Approach Book Chapter
Piotto, Stefano; Rossi, Federico; Concilio, Simona; Reverchon, Ernesto; Cattaneo, Giuseppe (Ed.): Chapter 1, pp. 3-10, Springer International Publishing AG 2018, 2017, ISBN: 978-3-319-62026-8.
Abstract | Links | BibTeX | Tags: liposome
@inbook{Bochicchio2017b,
title = {Nanoliposomes Production by a Protocol Based on a Simil-Microfluidic Approach},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Federica Recupido and Gaetano Lamberti and Anna Angela Barba},
editor = {Stefano Piotto and Federico Rossi and Simona Concilio and Ernesto Reverchon and Giuseppe Cattaneo},
url = {https://link.springer.com/chapter/10.1007/978-3-319-62027-5_1},
publisher = {Springer International Publishing AG 2018},
series = {Lecture Notes in Bioengineering book},
abstract = {In this work a protocol based on the microfluidic principles has been developed and applied to produce nanoliposomes. The protocol basically consists in the realization of a contact between two flows, lipids/ethanol and water solutions, inside a tubular device where interdiffusion phenomena allow the formation of lipid vesicles. Effects of solutions flow rates and lipids concentrations on size and size distribution have been investigated. Moreover, ultrasonic energy was used to enhance homogenization of the hydroalcoholic final solutions and to promote the vesicles size reduction. By this protocol a massive output has been achieved; increasing the ratio between the water volumetric flow rate to the lipids-ethanol volumetric flow rate the liposomes dimension decreases; at equal flow rates, when the lipids concentration increases also the liposomes size has been observed increasing. },
keywords = {liposome},
In this work a protocol based on the microfluidic principles has been developed and applied to produce nanoliposomes. The protocol basically consists in the realization of a contact between two flows, lipids/ethanol and water solutions, inside a tubular device where interdiffusion phenomena allow the formation of lipid vesicles. Effects of solutions flow rates and lipids concentrations on size and size distribution have been investigated. Moreover, ultrasonic energy was used to enhance homogenization of the hydroalcoholic final solutions and to promote the vesicles size reduction. By this protocol a massive output has been achieved; increasing the ratio between the water volumetric flow rate to the lipids-ethanol volumetric flow rate the liposomes dimension decreases; at equal flow rates, when the lipids concentration increases also the liposomes size has been observed increasing.
https://link.springer.com/chapter/10.1007/978-3-319-62027-5_1
doi:10.1007/978-3-319-62027-5_1
Dalmoro, Annalisa; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides Journal Article
Natural Product Communications, 12 (6), pp. 863-866, 2017, ISSN: 1934-578X.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors, microencapsulation, ultrasonic atomization
@article{NPC01,
title = {Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides},
author = {Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.naturalproduct.us/index.asp
https://www.gruppotpp.it/wp-content/uploads/2017/06/Dalmoro-et-al-NPC-126-863-866-2017-Abstract-1.pdf},
journal = {Natural Product Communications},
abstract = {This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).},
keywords = {Micro and Nano Vectors, microencapsulation, ultrasonic atomization},
This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).
http://www.naturalproduct.us/index.asp
https://www.gruppotpp.it/wp-content/uploads/2017/06/Dalmoro-et-al-NPC-126-863-86[...]
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela
Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article
Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling
title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba},
https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf},
abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems' behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling},
Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems' behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-87[...]
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Central Composite Design in HPMC granulation and correlations between product properties and process parameters Journal Article
New Journal of Chemistry, 41 (14), pp. 6504-6513, 2017.
title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract},
doi = {10.1039/C7NJ01280B},
abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.},
Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.
http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract
doi:10.1039/C7NJ01280B
Caccavo, Diego; Cascone, Sara; Poto, Serena; Lamberti, Gaetano; Barba, Anna Angela
Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests Journal Article
Carbohydrate Polymers, 167 , pp. 136–144, 2017.
title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests},
author = {Diego Caccavo and Sara Cascone and Serena Poto and Gaetano Lamberti and Anna Angela Barba},
abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels' behavior. },
Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels' behavior.
Bochicchio, Sabrina; Dapas, Barbara; Russo, Ilaria; Ciacci, Carolina; Piazza, Ornella; De Smedt, Stefan ; Pottie, Eline; Barba, Anna Angela; Grassi, Gabriele
In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer Journal Article
title = {In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer},
author = {Sabrina Bochicchio and Barbara Dapas and Ilaria Russo and Carolina Ciacci and Ornella Piazza and Stefan {De Smedt} and Eline Pottie and Anna Angela Barba and Gabriele Grassi},
abstract = {Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour.
siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.},
Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour.
siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.
Barba, Anna Angela; Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Chiarappa, Gianluca; Abrami, Michela; Grassi, Gabriele; Grassi, Mario; Tomaiuolo, Giovanna; Guido, Stefano; Brucato, Valerio; Carfì Pavia, Francesco ; Ghersi, Giulio; La Carrubba, Vincenzo ; Abbiati, Roberto Andrea; Manca, Davide
Engineering approaches in siRNA delivery Journal Article
title = {Engineering approaches in siRNA delivery},
author = {Anna Angela Barba and Sara Cascone and Diego Caccavo and Gaetano Lamberti and Gianluca Chiarappa and Michela Abrami and Gabriele Grassi and Mario Grassi and Giovanna Tomaiuolo and Stefano Guido and Valerio Brucato and Francesco {Carf\`{i} Pavia} and Giulio Ghersi and Vincenzo {La Carrubba} and Roberto Andrea Abbiati and Davide Manca},
abstract = {siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors' production processes and siRNAs vectors' release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors' fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.},
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors' production processes and siRNAs vectors' release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors' fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.
Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Maria Grazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose Journal Article
Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization
@article{Kazlauske2017,
title = {Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose},
author = {Jurgita Kazlauske and Maria Margherita Cafaro and Diego Caccavo and Maria Grazia Marucci and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
abstract = {The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.},
keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization},
The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.
Caccavo, Diego; Lamberti, Gaetano; Cafaro, Maria Margherita; Barba, Anna Angela; Kazlauske, Jurgita; Larsson, Anette
Mathematical modeling of the drug release from an ensemble of coated pellets Journal Article
British Journal of Pharmacology, 174 (12), pp. 1797–1809 , 2017, ISBN: 1476-5381.
Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling
title = {Mathematical modeling of the drug release from an ensemble of coated pellets},
author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson},
url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract},
doi = {10.1111/bph.13776},
isbn = {1476-5381},
journal = {British Journal of Pharmacology},
pages = {1797\textendash1809 },
abstract = {Background and Purpose
Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.
Experimental approach
In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.
Key Results
In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.
Conclusions and Implications
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.},
keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling},
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.
http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract
doi:10.1111/bph.13776
Dalmoro, Annalisa; Sitenkov, Alexander Y; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method Journal Article
International Journal of Pharmaceutics, 518 (1-2), pp. 50–58, 2017.
title = {Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method},
author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
pages = {50\textendash58},
abstract = {In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%.
Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.},
In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%.
Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.
Barba, Anna Angela; Grassi, Gabriele; Grassi, Mario; Lamberti, Gaetano
New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery Journal Article
Current Drug Delivery, 14 (2), pp. 156-157, 2017.
title = {New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery},
author = {Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/01.-Barba-et-al-CDD-142-156-157-2017.pdf
http://www.eurekaselect.com/149727},
doi = {10.2174/156720181402170202202808},
journal = {Current Drug Delivery},
abstract = {Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and
only if effective delivery systems are available. Among NABDs, small interfering RNAs (siRNAs) show revolutionary potentiality
due to the ability to silencing the expression of gene-causing diseases. Thus, siRNA drugs have huge therapeutic potentials,
even in the treatment of life threatening diseases. However, the use of siRNAs is limited because of some inconveniences:
they are large macromolecules, negatively charged, undergo rapid degradation by plasma enzymes, are subjected to fast renal
clearance/hepatic sequestration and can hardly cross cellular membranes. These aspects seriously impair siRNAs usability as
therapeutics. To overcome these obstacles, the scientific problem has to be faced out through a multidisciplinary approach, integrating
all relevant and necessary expertise. In this Full-Thematic Issue of the Current Drug Delivery, the development of
siRNAs delivery approaches is described from different points of view by several research groups, which have been jointly
working on the subject in the last years.
The Thematic Issue starts with the paper by Chiarappa et al., devoted to describe the potentiality of the Chemical Engineering
expertise in the "Bio world" through reminding the foundation of Biological Engineering (BE) that develops, with its current
and multidisciplinary approaches, winning strategies in modern research. The concepts of unit operations and transport
phenomena, with which chemical engineers are confident, are applied to the description of the biomedical/pharmaceutical
world and to the study of siRNAs delivery, in order to get a better understanding and description of how biological systems
The engineering approach to siRNA delivery is, then, reported analyzing two topics. In particular, the paper by Caccavo
et al. deals with the modeling of hydrogel based drug delivery systems, materials widely used in controlled drug delivery,
which could be adopted also for siRNAs delivery. Abbiati and Manca report the use of a physiologically-based pharmacokinetic
model, useful in order to assess the fate of drugs, including siRNAs, once administered. The novel preparative methods to
be used in siRNAs delivery are the subjects of the paper by Bochicchio et al., focusing on both the lipid-based and the polymerbased
carriers. More specifically, Dalmoro et al. discuss the use of injectable chitosan/β-glycerophosphate systems, whereas
Cavallaro et al. report the uses of polycation-based smart carriers for siRNAs delivery. Advanced testing methods for the study
of drug delivery systems and the interactions between delivery systems and living systems are discussed in the paper by
D'Apolito et al. and Carf\`{i}-Pavia et al. D'Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carf\`{i}-Pavia
et al. concentrate the attention on a novel bioreactor able to mimic the vascular behavior for in-vitro tests of drug delivery. Last
but not the least, the medical applications of novel delivery systems and siRNAs are discussed in the paper by Piazza et al.,
focusing on the delivery of siRNAs by liposomes in order to silence cycline D1 in ex-vivo human tissues. Moreover, the paper
by Di Gioia et al., deals with the siRNAs' based therapies against inflammatory respiratory diseases, while the paper by Farra
et al., discusses the role of the transcription factor E2F1 in hepatocellular carcinoma and the opportunity of its silencing by siRNAs.
In conclusion, the papers presented strongly indicate that only a multidisciplinary approach can successfully overcome the
still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential.},
Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and
D'Apolito et al. and Carfì-Pavia et al. D'Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carfì-Pavia
still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential.
https://www.gruppotpp.it/wp-content/uploads/2017/03/01.-Barba-et-al-CDD-142-156-[...]
http://www.eurekaselect.com/149727
doi:10.2174/156720181402170202202808
Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Barba, Anna Angela; Boisen, Anja; Brucato, Valerio; Ghersi, Giulio; Caccavo, Diego; Cascone, Sara; Caserta, Sergio; Elvassore, Nicola; Giomo, Monica; Guido, Stefano; Lamberti, Gaetano; Larobina, Domenico; Manca, Davide; Marizza, Paolo; Tomaiuolo, Giovanna; Grassi, Gabriele
Chemical Engineering in the "BIO" world Journal Article
Current Drug Delivery, 14 (2), pp. 158 - 178, 2017.
Abstract | Links | BibTeX | Tags:
@article{Chiarappa2016,
title = {Chemical Engineering in the "BIO" world},
author = {Gianluca Chiarappa and Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Anna Angela Barba and Anja Boisen and Valerio Brucato and Giulio Ghersi and Diego Caccavo and Sara Cascone and Sergio Caserta and Nicola Elvassore and Monica Giomo and Stefano Guido and Gaetano Lamberti and Domenico Larobina and Davide Manca and Paolo Marizza and Giovanna Tomaiuolo and Gabriele Grassi },
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-158-178-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/158/},
doi = {10.2174/1567201813666160602230550},
issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},
pages = {158 - 178},
abstract = {Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.},
Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.
https://www.gruppotpp.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-[...]
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/[...]
doi:10.2174/1567201813666160602230550
Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
New preparative approaches for micro and nano drug delivery carriers Journal Article
title = {New preparative approaches for micro and nano drug delivery carriers},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/05.-Bochicchio-et-al-CDD-142-203-215-2017.pdf
abstract = {The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings.
In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.},
The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings.
In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.
https://www.gruppotpp.it/wp-content/uploads/2017/03/05.-Bochicchio-et-al-CDD-142[...]
Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico
Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests Journal Article
Abstract | Links | BibTeX | Tags: Hydrogel Characterization
title = { Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests},
author = {Annalisa Dalmoro and Michela Abrami and Barbara Galzerano and Sabrina Bochicchio and Anna Angela Barba and Mario Grassi and Domenico Larobina},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-216-223-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/216/
abstract = {Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.},
keywords = {Hydrogel Characterization},
Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.
https://www.gruppotpp.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-21[...]
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Drug delivery from hydrogels: a general framework for the release modeling Journal Article
Abstract | Links | BibTeX | Tags: Hydrogel Modeling
title = {Drug delivery from hydrogels: a general framework for the release modeling},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf
abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.},
keywords = {Hydrogel Modeling},
The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.
https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-17[...]
Abstract | Links | BibTeX | Tags: Biodistribution, In vitro, Pharmacokinetics
keywords = {Biodistribution, In vitro, Pharmacokinetics},
Lamberti, Gaetano; Barba, Anna Angela; Cascone, Sara; Dalmoro, Annalisa; Caccavo, Diego
An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications Book Chapter
Majee, Sutapa Biswas (Ed.): Emerging Concepts in Analysis and Applications of Hydrogels, Chapter 8, Intech, 2016, ISBN: 978-953-51-2510-5.
@inbook{Lamberti2016b,
title = {An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications},
author = {Gaetano Lamberti and Anna Angela Barba and Sara Cascone and Annalisa Dalmoro and Diego Caccavo},
editor = {Sutapa Biswas Majee},
url = {http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/an-engineering-point-of-view-on-the-use-of-the-hydrogels-for-pharmaceutical-and-biomedical-applicati},
doi = {10.5772/64299 },
isbn = {978-953-51-2510-5},
booktitle = {Emerging Concepts in Analysis and Applications of Hydrogels},
publisher = {Intech},
abstract = {In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.},
In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.
http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-o[...]
doi:10.5772/64299
Abstract | Links | BibTeX | Tags: In silico, Pharmacokinetics
keywords = {In silico, Pharmacokinetics},
Dalmoro, Annalisa; Barba, Anna Angela; Grassi, Gabriele; Grassi, Mario; Lamberti, Gaetano
In situ coronary stent paving by Pluronic F127–alginate gel blends: formulation and erosion tests Journal Article
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 104 (5), pp. 1013-22, 2016.
Abstract | Links | BibTeX | Tags: coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends
title = {In situ coronary stent paving by Pluronic F127\textendashalginate gel blends: formulation and erosion tests},
author = {Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti},
url = {http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33425/abstract;jsessionid=31C6676EE270B6362CB149075EE37B5F.f01t01},
doi = {10.1002/jbm.b.33425},
journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials},
pages = {1013-22},
abstract = {In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.},
keywords = {coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends},
In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33425/abstract;jsessionid=31C66[...]
doi:10.1002/jbm.b.33425
Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Gabriele; Lamberti, Gaetano
Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation Journal Article
LWT - Food Science and Technology, 69 , pp. 9-16, 2016.
title = {Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation},
author = {Sabrina Bochicchio and Anna Angela Barba and Gabriele Grassi and Gaetano Lamberti},
doi = {10.1016/j.lwt.2016.01.025},
journal = {LWT - Food Science and Technology},
abstract = {In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.},
In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.
doi:10.1016/j.lwt.2016.01.025
Dalmoro, Annalisa; Sitenkov, Alexander Y; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell–core microparticles Journal Article
Journal of Applied Polymer Science, 133 (42976), 2016.
title = {Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell\textendashcore microparticles},
author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
url = {http://onlinelibrary.wiley.com/doi/10.1002/app.42976/abstract},
number = {42976},
abstract = {In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell\textendashcore microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization\textendashpolyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers. },
In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell–core microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization–polyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers.
http://onlinelibrary.wiley.com/doi/10.1002/app.42976/abstract
Swellable Hydrogel-based Systems for Controlled Drug Delivery Book Chapter
Sezer, Ali Demir (Ed.): Smart Drug Delivery System, Chapter 10, Intech, 2016, ISBN: 978-953-51-2247-0.
title = {Swellable Hydrogel-based Systems for Controlled Drug Delivery},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
editor = {Ali Demir Sezer},
url = {http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-based-systems-for-controlled-drug-delivery#exportas},
doi = {10.5772/61792},
booktitle = {Smart Drug Delivery System},
abstract = {The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass\textendashrubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, "eroding" the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.},
The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass–rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, "eroding" the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.
http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-ba[...]
Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette
Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment Journal Article
Carbohydrate Polymers, 131 , pp. 41–49, 2015, ISSN: 01448617.
Abstract | Links | BibTeX | Tags: Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport
title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment},
author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson},
abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.},
keywords = {Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport},
The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.