Interleukin10 Microsphere in Inflammatory Bowel Disease

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The cytokine Interleukin-10 (IL-10) has shown promise in clinical trials for the treatment of inflammatory bowel disease (IBD). Currently IL-10 is administered to IBD patients systemically either by bolus intravenous or subcutaneous injections. Due to the short in vivo half-life of IL-10, repeated injections of high doses of IL-10 over a period of several weeks is required for efficacy. In this proposal, a novel delivery technology for the sustained release of low-dose Interleukin-10 (IL-10) directly to the gastrointestinal tract is tested in a murine model of IBD. IL-10 is encapsulated into biodegradable polymer microspheres which are specifically formulated to achieve a strong adhesion to the intestinal epithelium and are administered orally to IL-10 knock-out mice which spontaneously develop chronic enterocolitis. The ability of IL-10 that is released in a sustained fashion from the bioadhesive microspheres in the GI tract to suppress inflammation and ameliorate disease is then evaluated in two different embodiments of the murine model. In Aim 1, the ability of IL-10-loaded bioadhesive microspheres to prevent the development of disease is compared to that of bolus systemic IL-10 administration in young mice. In Aim 2, the efficacy of IL-10 microspheres to suppress established disease is evaluated and compared to bolus systemic IL-10 therapy in adult mice. If successful, our novel delivery system will provide a more clinically feasible and effective alternative to bolus injections of soluble IL-10 for the treatment of IBD. PROPOSED COMMERCIAL APPLICATIONS: The commercial application of orally administered IL-10-encapsulated biodegradable microspheres for treatment of inflammatory bowel disease is readily apparent. If proven effective, this approach will provide a simple, effective and more clinically feasible alternative to parenteral administration of soluble IL-10. T & B Bioclone intends to pursue the clinical use of the IL-10 microsphere technology for therapy of IBD in collaboration with our collaborators at Brown University.