# HYDROGEL BEADS WITH SELF-REGULATING MICROCLIMATE PH PROPERTIES 

## CROSS-REFERENCE TO RELATED APPLICATIONS 

[0001] This application claims priority to U.S. Provisional Application Ser. No. 62/381,748 filed on Aug. 31, 2016, and U.S. Provisional Application Ser. No. 62/402,017 filed on Sep. 30, 2016, which are incorporated herein by reference in their entirety. 

## STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH & DEVELOPMENT 

[0002] This invention was made with govermnent support under 2014-67017-21635 and 2016-31100-06025 awarded by the USDA, National Institute of Food and Agriculture (NIFA). The government has certain rights in the invention. 

[0003] The present disclosure is related to hydrogel beads, specifically hydrogel beads for delivery ofbioactive agents. 

[0004] There is considerable interest in the development of colloidal delivery systems to encapsulate, protect and deliver bioactive agents (nutrients, micronutrients, nutraceu› ticals, and drugs) in the food, supplement, and pharmaceu› tical industries. Numerous types of bioactive agents can be encapsulated and delivered such as proteins, peptides, amino acids, probiotics, prebiotics, vitamins, minerals, nutraceuti› cals, triacylglycerol oils, flavors, colors, antimicrobials, pre› servatives, and the like. For example, bioactive proteins are often encapsulated due to their sensitivity to chemical deg› radation and their potential for causing off-flavors (such as bitterness or astringency). Probiotic bacteria can be pro› tected from acidic stomach conditions as they move through the gastrointestinal tract (GIT) to areas where their benefi› cial actions are most effective (such as the colon). Many lipophilic bioactive agents (e.g., curcumin and carotenoids) are encapsulated to address the limitations of their incorpo› ration into food products such as low water-solubility, poor chemical instability, and low bioaccessibility. Many natural colors and flavors are encapsulated to inhibit their chemical degradation under unfavorable environmental conditions. 

[0005] Research has indicated that encapsulation in col› loidal delivery systems can improve the handling, applica› bility, chemical stability, and oral bioavailability of many bioactive agents. Colloidal delivery systems may be fabri› cated using different procedures and methods based on the molecular and physicochemical properties of the bioactive agents. One of the most promising approaches to create colloidal delivery systems is to fabricate hydrogel beads with bioactive agents trapped inside. Hydrogel beads nor› mally contain hydrophilic, porous, and elastic polymer matrices, which can improve the stability ofbioactive agents during storage and control their release after oral intake. Because hydrogel beads are formed using mild preparation conditions with food-grade biopolymers (e.g., polysaccha› rides and protein) that do not usually adversely affect the properties of encapsulated bioactive agents, they can be found in the applications of a broad range fields from food to medicine. 

## FIELD OF THE DISCLOSURE 

## BACKGROUND 

[0006] Many bioactive agents are highly susceptible to physical, chemical or biological degradation under one set of pH conditions, but are relatively stable under another set of pH conditions. For example, some natural colors rapidly fade under highly acidic pH conditions, but slowly under neutral conditions. Many probiotics (bacteria beneficial to gut health) are rapidly inactivated under highly acidic con› ditions, but remain viable under neutral conditions. A major drawback associated with the use of conventional hydrogel beads for the encapsulation of these pH-labile bioactive agents is that they are highly porous, and so acid or alkaline determining ions (such as H+ or OH-) can easily diffuse in or out of them, thereby causing the pH inside the beads to be fairly similar to that outside. As a result, any pH-labile bioactive agents may be readily degraded when they are encapsulated in this type of bead. The pH sensitivity of conventional hydrogel beads therefore hinders their wide› spread applications in the food, supplement, and pharma› ceutical industries for encapsulating pH-labile bioactive agents. 

[0007] Research has been carried out to improve the pH-stability of substances encapsulated in hydrogel beads, e.g., by coating the beads with one or more layers of biopolymers using electrostatic deposition, or by crosslink› ing the hydrogel matrix using specific enzymes. These approaches are based on delaying the diffusion of pH determining ions into the hydrogel beads. However, these approaches have been shown to have a limited protective effect and also have other limitations, i.e., the fabrication procedure is complex and the encapsulated bioactive agents are not released at the desired site of action. 

[0008] What is needed are new strategies for providing hydrogel beads that can improve the stability of encapsu› lated bioactive agents. 

[0009] In one aspect, a composition comprises a hydrogel bead in an external matrix, the hydrogel bead comprising an at least partially crosslinked gelling polymer, the hydrogel bead having encapsulated therein a functional agent, and a buffering agent having low water solubility, wherein at least a portion of the buffering agent is in solid form in the hydrogel bead. 

[0010] In another aspect, also included are pharmaceutical and food compositions comprising the hydrogel beads. 

[0011] In yet another aspect, a method of making an encapsulated functional agent comprises mixing a gelling polymer, a functional agent, and a buffering agent having low water solubility to form a mixture, forming hydrogel beads from the mixture, and crosslinking at least a portion of the gelling polymer in the hydro gel beads to provide the encapsulated functional agent, wherein at least a portion of the buffering agent is in solid form in the hydrogel bead. 

## BRIEF DESCRIPTION OF THE DRAWINGS 

[0012] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be pro› vided by the Office upon request and payment of the necessary fee. 

[0013] FIG. 1 is a schematic diagram showing the fabri› cation of self-adjusting microclimate pH hydro gel beads; the 

## BRIEF SUMMARY 

