Interleukin10 Microsphere in Inflammatory Bowel Disease

细胞因子白细胞介素-10（IL-10）在临床试验中显示出治疗炎症性肠病（IBD）的前景。目前，IL-10通过静脉内推注或皮下注射全身性地施用于IBD患者。由于IL-10的体内半衰期短，需要在几周的时间内重复注射高剂量的IL-10以获得功效。在该提议中，在IBD的鼠模型中测试了用于直接向胃肠道持续释放低剂量白细胞介素-10（IL-10）的新型递送技术。IL-10被封装到生物可降解的聚合物微球中，该微球被特别配制以实现对肠上皮的强粘附，并且被口服施用给自发发展慢性小肠结肠炎的IL-10敲除小鼠。然后在鼠模型的两个不同实施方案中评价IL-10在胃肠道中以持续方式从生物粘附性微球释放以抑制炎症和改善疾病的能力。在目的1中，将负载IL-10的生物粘附性微球预防疾病发展的能力与在年幼小鼠中推注全身性IL-10施用的能力进行比较。在目的2中，评估IL-10微球抑制已建立疾病的功效，并与成年小鼠中的推注全身IL-10疗法进行比较。如果成功的话，我们的新型递送系统将提供一种临床上更可行和有效的替代可溶性IL-10的推注用于治疗IBD。拟议的商业应用：口服给药的IL-10包封的生物可降解微球用于治疗炎性肠病的商业应用是显而易见的。如果证明有效，这种方法将提供一种简单、有效和临床上更可行的替代胃肠外施用可溶性IL-10的方法。T & B Bioclone打算与我们在布朗大学的合作者合作，寻求IL-10微球技术在IBD治疗中的临床应用。

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.