IMPLANTABLE BIODEGRADABLE CAPSULES FOR PROTEIN DELIVERY

BIOTEK提出开发一种新方法，用于将药物纳入适合延长储药输送的植入式系统。该技术简单，温和，有效，其成功的开发和商业化可以提供第一条途径，一个通用的长期肠胃外输送系统的治疗蛋白质和肽。该方法通过非常高分子量的聚-L-丙交酯的可用性而成为可能，所述聚-L-丙交酯是一种聚合物，即使作为薄壁胶囊，也保持足够的强度以允许早期手术移除，但是一旦递送完成，其再吸收而不需要手术。该工艺产率高，并且不会将药物暴露于溶剂或苛刻条件下，因此特别适用于不稳定或昂贵的药物，如蛋白质。在第I阶段，BIOTEK将制备和表征含和不含孔隙增强剂的胶囊，测量拉伸强度和爆破强度，用各种酶蛋白装载胶囊，在体外进行总递送，确认释放蛋白的活性，研究植入和取出的难易程度，并研究家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。基于该信息，将选择药用肽或蛋白质用于II期期间的初始产品开发，其将包括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：将蛋白质和肽配制成能够延长递送的可生物降解的植入物的经济、安全和有效的方法将消除对频繁注射此类药物的需要，并且类似的方法应该可以应用于其他有效化合物如类固醇和阿糖胞苷的长期递送。

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.