Peptide Crosslinked Poly(Lactide-co-Glycolide) (PLGA) nanoparticles for drug depot formulations

用于药物储库制剂的肽交联聚丙交酯-乙交酯 (PLGA) 纳米颗粒

• 批准号: 531032-2018
• 负责人: Ahmed, Marya
• 金额: $ 1.82万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=643571
• 关键词: Peptide; Crosslinked; Poly; Lactide; co

Poly(lactide-co-glycolide) (PLGA), a FDA approved biodegradable polymer, is well-studied to deliver drugs in**laboratory and clinical settings and is the focus of attention of Biovectra to manufacture Health Canada (HC)**approved drug depot formulations. The physiochemical properties of PLGA, such as polymer molecular**weight, lactide to glycolide ratio, cross-linking density, size of nanoparticles and their surface chemistry are**some techniques that have been investigated to prepare controlled drug release formulations. However, these**modifications do not always satisfy critical safety standards required by health authorities like FDA and hence**are of less interest to pharmaceutical companies such as Biovectra. In this proposal, we aim to develop PLGA**based nanoparticles for prolonged drug release, using PLGA, collagen peptide conjugates in the presence of**FDA approved, cross-linker, 5'-riboflavin phosphate. 5'-riboflavin phosphate is biocompatible cross-linker,**used for ocular therapies to crosslink the retina of patients by UV induced cross-linking of collagen peptides.**Taking advantage of biocompatible properties of PLGA, 5'-riboflavin phosphate and collagen peptide, we aim**to prepare PLGA based cross-linked nanoparticles by facile conjugation of collagen peptide to PLGA**copolymers, followed by their cross-linking and nanoprecipitation in the form of nanoparticles, in the presence**of drug. The nanoparticles produced will be tested for their drug release profiles under physiological conditions**and will be evaluated for their toxicities during in vitro studies.

聚（丙交酯-共-乙交酯）（PLGA）是FDA批准的生物可降解聚合物，在 ** 实验室和临床环境中进行了充分的研究，是Biovectra生产加拿大卫生部（HC）** 批准的药物贮库制剂的关注焦点。PLGA的物理化学性质，如聚合物分子量、丙交酯与乙交酯的比例、交联密度、纳米颗粒的大小及其表面化学是一些已经被研究用于制备药物控释制剂的技术。然而，这些 ** 修改并不总是满足FDA等卫生当局要求的关键安全标准，因此 ** 对Biovectra等制药公司不太感兴趣。在该提案中，我们的目标是开发基于PLGA** 的纳米颗粒，用于延长药物释放，在 **FDA批准的交联剂5 '-核黄素磷酸盐的存在下使用PLGA胶原肽缀合物。5 '-核黄素磷酸盐是生物相容性交联剂，** 用于眼部治疗，通过紫外线诱导胶原肽交联患者的视网膜。**利用PLGA、5 '-核黄素磷酸盐和胶原蛋白肽的生物相容性，我们的目标是 ** 通过胶原蛋白肽与PLGA** 共聚物的简单缀合，然后在药物存在下以纳米颗粒的形式交联和纳米沉淀来制备基于PLGA的交联纳米颗粒。生产的纳米颗粒将在生理条件下测试其药物释放曲线 **，并将在体外研究期间评估其毒性。