1. Technical Field of the Invention
The present invention relates to the use of mesoporous compositions for use in drug delivery systems.
2. Description of the Prior Art
Porous substances are generally divided by pore size. For example, those having pore sizes smaller than 2 nm are classified as microporous substances, between 2 and 50 nm are classified as mesoporous substances and larger than 50 nm are classified as macroporous substances. Because of the range of their pore sizes, mesoporous materials are compatible with applications such as separation or sensing of relatively large-organic molecules. Typical of the mesoporous materials are amorphous or polycrystalline solids such as pillared clays and silicates. Unfortunately, the pores in these materials are often irregularly spaced and broadly distributed in size.
There is growing interest in the use of inorganic materials as host matrices for bioactive molecules. The principal advantages of such host/guest type materials include the stability and relative inertness of the materials as well as their easy transportation as free flowing powders. Considerable synthetic effort has therefore been devoted to developing molecular sieve frameworks with pore diameters within the mesoporous range, and the development of a series of molecular sieves having a hexagonal array of uniform mesopores has been reported. A group of researchers at Mobil Oil Corporation have reported a series of mesoporous molecular sieves, named MCM-41, in U.S. Pat. Nos. 5,057,296 and 5,102,643, which are fully incorporated by reference. According to these patents, MCM-41 has a structure exhibiting hexagonal arrangement of straight channels, such as a honeycomb, on a silica plate. MCM-41 is synthesized using the cationic type surfactant, quaternary alkyltrimethylammonium salts [CnH2n+1(CH3)3N+X−] and various silica sources, like sodium silicates, tetraethyl orthosilicate, or silica gel, under hydrothermal conditions. On the other hand, the mesoporous materials in the SBA series, another group of synthetic mesoporous materials, are synthesized using neutral templates (Zhao et. al., Science 279, 548 (1998)).
MCM-41 synthesis has been proposed to occur through a liquid crystal templating mechanism. Researchers have proposed that the structure is defined by the organization of surfactant molecules into liquid crystals which serve as templates for the formation of the MCM-41 structure. (Beck et. al., J. Am. Chem. Soc. 114, 10834 (1992), fully incorporated by reference herein). In other words, the first step in the synthesis would correspond to the formation of a micellar rod around the surfactant micelle, which in a second step will produce a hexagonal array of rods, followed by incorporation of an inorganic array (like silica, or silica-alumina) around the rodlike structures. That is, in an aqueous solution, surfactants form a liquid crystal structure which is surrounded by silicate ions and the liquid crystal structure is associated with MCM-41 substance via a hydrothermal reaction and then, removed by calcination at a temperature of 500 to 600° C., to prepare MCM-41.
MCM-41 has been actively researched for characterization and application by many laboratories, because their large and uniform pore sizes allow the entry of otherwise sterically hindered molecules. The pore size of MCM-41 can be adjusted in a range of from 1.6 nm up to 10 nm by modulating the kinds of surfactants or synthesis conditions. Additionally, the easily tailored pore size and availability of compositional variance, provides a versatile range of materials for applications that span from catalysis to drug delivery.
The mesoporous compositions of the present invention are synthesized using a novel templating molecule, vitamin E, which renders the mesoporous compositions of the present invention unique over those described in the art.
A composition comprising vitamin E and silica is taught in U.S. Pat. No. 5,234,695, which is fully incorporated by reference in the disclosure. The invention contemplates the addition of a flow agent to a water dispersible vitamin E composition, where the flow agent is preferably fumed silica having an average particle size of about 0.1 micron. This composition comprises vitamin E and silica and lacks any definite form i.e., represents an amorphous composition.
The composition of the present invention is unique over the amorphous composition described in U.S. Pat. No. 5,234,695, in that said composition is a mesoporous molecular sieve, comprising alumina (Al2O3) and vitamin E.
Drug insolubility is one of the most challenging issues in the development of many pharmaceutical products. Over one third of the drugs listed in the U.S. Pharmacopoeia and about 50% of new chemical entities are insoluble or poorly soluble in water. As a result, many drugs are marketed as sub-optimal formulations, often giving poor or erratic bioavailability or a greater risk of adverse side effects. Certain aspects of the claimed invention can be used to facilitate the in situ delivery of insoluble or poorly soluble drugs by using a vitamin E TPGS micelle as a host for the delivery of guest molecules.