Interleukin10 Microsphere in Inflammatory Bowel Disease

白细胞介素10微球在炎症性肠病中的应用

• 批准号: 6405478
• 负责人: NEJAT K EGILMEZ
• 金额: $ 9.95万
• 依托单位: T AND B BIOCLONE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6405478
• 关键词: antiinflammatory agents; biodegradable product; cytokine; drug delivery systems; drug design /synthesis /production; inflammatory bowel diseases; interleukin 10; laboratory mouse; microcapsule

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.

细胞因子白介素 10 (IL-10) 在治疗炎症性肠病 (IBD) 的临床试验中显示出良好的前景。目前，IL-10通过静脉推注或皮下注射全身给药于IBD患者。由于IL-10体内半衰期短，需要在几周内重复注射高剂量的IL-10才能发挥功效。在该提案中，在 IBD 小鼠模型中测试了一种将低剂量白细胞介素 10 (IL-10) 直接持续释放到胃肠道的新型递送技术。 IL-10 被封装在可生物降解的聚合物微球中，该微球经过专门配制，可实现与肠上皮的牢固粘附，并给自发发展为慢性小肠结肠炎的 IL-10 敲除小鼠口服给药。然后在小鼠模型的两个不同实施例中评估从胃肠道中的生物粘附微球以持续方式释放的IL-10抑制炎症和改善疾病的能力。在目标 1 中，将负载 IL-10 的生物粘附微球预防疾病发展的能力与在年轻小鼠中全身推注 IL-10 的能力进行了比较。在目标 2 中，评估了 IL-10 微球抑制已确定疾病的功效，并与成年小鼠中推注全身 IL-10 疗法进行比较。如果成功，我们的新型输送系统将为可溶性 IL-10 的推注注射提供一种临床上更可行、更有效的替代方案，用于治疗 IBD。拟议的商业应用：口服IL-10封装的生物可降解微球用于治疗炎症性肠病的商业应用是显而易见的。如果被证明有效，这种方法将为可溶性 IL-10 的胃肠外给药提供一种简单、有效且临床上更可行的替代方案。 T & B Bioclone 打算与布朗大学的合作者合作，探索 IL-10 微球技术在 IBD 治疗中的临床应用。