Cross-linked polyester-based depot systems for sustained drug delivery: determining the relationship between composition, properties and performance

目前有超过20种药物产品，包括可植入、可插入或可注射的药物输送系统，这些系统由共聚物聚（丙交酯-羟基乙酸酯）（PLGA）形成，并随着时间的推移提供药物治疗的持续释放。单次给药即可实现持续的药物释放，无需每天或每周给药，因此对患者的生活质量和患者依从性产生了深远的积极影响，并显著降低了医疗保健成本。这些产品目前用于治疗重症疾病，包括糖尿病、子宫内膜异位症、前列腺癌和精神分裂症。虽然基于plga的系统已经为许多药物提供了一种输送解决方案，但很明显，需要一种新的聚合物输送系统来满足制药行业的需求。鉴于每种药物在其物理化学性质方面都是独特的，并且聚合物-药物相互作用和相容性是影响聚合物递送配方性能的关键指标，因此没有一种聚合物可以作为所有药物配方的通用材料。出于这个原因，Pendant Biosciences（一家加拿大公司）已经获得了专利，并与allen实验室合作提交了一份额外的临时专利申请，该专利涉及一种柔性聚合物平台，该平台包括公认的构建块，可生产交联生物相容性系统，用于长时间递送各种药物。如果成功，拟议的研究将导致(1)鉴定一种主要的药物-聚合物产品，供Pendant Biosciences开发；(2)生物相容性聚合物材料的“工具箱”，以促进学术和工业环境中的药物递送研究；(3)提高对药物-聚合物组合产品性能的物理和化学指标的科学认识。

There are currently more than 20 pharmaceutical products that include implantable, insertable or injectabledrug delivery systems that are formed from the copolymer poly(lactide-co-glycolide) (PLGA) and providesustained release of drug therapy over time. The sustained drug release that is achieved with a singleadministration, eliminates the need for daily or weekly drug administrations and as a result has a profoundlypositive impact on a patient's quality of life, patient compliance and leads to significant reductions in healthcare costs. These products are currently used to treat critical medical conditions including diabetes,endometriosis, prostate cancer and schizophrenia. While PLGA-based systems have provided a deliverysolution to many drugs, it is clear, a new polymeric delivery system is needed to meet the needs of thepharmaceutical industry. Given that each drug is unique in terms of its physico-chemical properties and thatpolymer-drug interaction and compatibility are key metrics that influence the performance of polymericdelivery formulations there is no single polymer that can serve as a universal material for formulation of alldrugs. For this reason, Pendant Biosciences (a Canadian company) has patented, and in collaboration with theAllen laboratory filed an additional provisional patent application, on a flexible polymer platform that includesrecognized building blocks that produce cross-linked biocompatible systems for prolonged delivery of a widerange of drugs. If successful, the proposed research will result in (1) identification of a lead drug-polymerproduct for development by Pendant Biosciences; (2) a 'tool-box' of biocompatible polymer materials tofacilitate drug-delivery research in academic and industrial settings and (3) increased scientific awareness ofthe physical and chemical metrics responsible for the performance of a drug-polymer combination product.