IMPLANTABLE BIODEGRADABLE CAPSULES FOR PROTEIN DELIVERY

BIOTEK建议开发一种新方法，将药物纳入适合长时间仓库交付的植入式系统。该技术简单、温和、高效，其成功开发和商业化可能为治疗性蛋白质和肽的通用长期肠外给药系统提供第一条途径。这一过程是由非常高分子量的聚l -actide的可用性实现的，这种聚合物即使作为薄壁胶囊，也保持足够的强度，允许早期手术切除，但一旦输送完成，它就会重新吸收，不需要手术。该工艺产率高，而且不需要将药物暴露在溶剂或恶劣条件下，因此特别适用于不稳定或昂贵的药物，如蛋白质。在I期试验中，BIOTEK将制备和表征含和不含孔隙增强剂的胶囊，测量拉伸和破裂强度，用各种酶蛋白装载胶囊，跟踪体外总递送，确认释放蛋白的活性，研究植入和移除的难易程度，并研究兔的任何组织刺激反应。第一阶段旨在确认该方法的广泛实用性，并为持续3个月以上的持续交付提供证据。根据这些信息，将选择一种药用肽或蛋白质进行II期的初始产品开发，包括GMP生产、质量评估、稳定性测试、IND提交和初始人体测试。拟议的商业应用：一种经济、安全、有效的方法将蛋白质和多肽配制成能够长时间递送的可生物降解植入物，将消除对此类药物频繁注射的需要，并且类似的方法将应用于其他有效化合物（如类固醇和前列腺素）的慢性递送。

BIOTEK proposes to develop a new method for incorporating drugs into an implantable system suitable for prolonged depot delivery. The technique is simple, mild, and efficient, and its successful development and commercialization could provide the first route to a generic long-term parenteral delivery system for therapeutic proteins and peptides. The process is made possible by the availability of very high molecular weight poly-L-actide, a polymer which, even as a thin walled capsule, remains strong enough to permit early surgical removal, yet which resorbs with no need for surgery once delivery is complete. The process gives high yields and does not expose the drug to solvents or harsh conditions, making it particularly appropriate for unstable or costly drugs such as proteins. In Phase I BIOTEK will prepare and characterize capsules with and without porosity-enhancing agents, measure tensile and burst strength, load capsules with various enzymatic proteins, follow total delivery in vitro, confirm the activity of the released proteins, investigate the ease of implantation and removal, and investigate any tissue irritation response in rabbits. Phase I is intended to confirm the broad utility of the method and to provide evidence for continuous delivery lasting more than 3 months. On the basis of that information a medicinal peptide or protein will be selected for initial product development during Phase II, which will include GMP manufacture, quality assessment, stability testing, IND submission, and initial human testing. PROPOSED COMMERCIAL APPLICATIONS: An economical, safe and effective way to formulate proteins and peptides into biodegradable implants capable of prolonged delivery would eliminate the need for frequent injection for such drugs, and a similar method should find application for chronic delivery of other potent compounds such as steroids and prostaglandins.