Casein Coated CAP Particles for Oral Insulin Delivery

DESCRIPTION (provided by applicant): Parenteral administration of insulin via the subcutaneous route is the only commercially available therapy to treat insulin-dependent diabetes mellitus. Multiple daily injections are required to manage and maintain blood glucose control due to its relatively short duration of action (4 to 8 hours). Oral insulin would provide an attractive alternative. However, successful development of an oral insulin formulation has been hampered by the numerous and complex barriers to protein absorption inherent to the gastrointestinal tract. A novel delivery system has emerged that may overcome these obstacles. The design of this delivery system incorporates an understanding of the complex barriers to oral insulin absorption and results in the production of biodegradable, insulin-impregnated, calcium phosphate / polyethylene glycol microparticles coated with casein. The characterization of particle size and morphology, their associated physicochemical properties, and the critical factors affecting these parameters will assist in formula optimization and process development. Thus, the aims of Phase I are to prepare a lot of casein coated, insulin-laden microparticles utilizing the most current manufacturing process; to fully characterize them in terms of particle size, particle morphology, % loading of insulin, insulin activity, relative component composition, moisture content, stability against digestive enzymes, pH-dependent dissolution characteristics, and storage stability; and to demonstrate a dose-dependent reduction in blood glucose with concomitant increase in serum insulin levels in rodents. Furthermore, modification and adaptation of the delivery system to another orally challenged therapeutic protein, such as human growth hormone, would demonstrate general utility of the delivery system. The long-range goal of this research is to develop a novel, safe, efficacious, long-acting, oral delivery system for insulin demonstrating a dose dependency with reduced variability that may be applicable to other therapeutically relevant proteins.