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

聚(丙交酯-乙交酯)(PLGA)是FDA批准的一种可生物降解聚合物，在**实验室和临床环境中进行了广泛的药物输送研究，是BioVectra关注的焦点，以生产加拿大卫生部(HC)**批准的药物仓库配方。PLGA的物化性质，如聚合物的相对分子质量、丙交酯与乙交酯的比例、交联度、纳米粒子的大小及其表面化学是制备药物控释制剂的一些已被研究的技术。然而，这些**修改并不总是满足FDA等卫生当局所要求的关键安全标准，因此**对BioVectra等制药公司不太感兴趣。在这项提案中，我们的目标是开发基于PLGA**的纳米颗粒，用于延长药物释放，使用PLGA，胶原多肽结合物，在**FDA批准的交联剂，5‘-核黄素磷酸存在的情况下。5‘-核黄素磷酸是一种生物相容性交联剂，**用于眼科治疗，通过紫外线诱导的胶原肽交联患者的视网膜。**利用PLGA、5’-核黄素磷酸和胶原肽的生物相容性，我们的目标是**在药物的存在下，通过胶原肽与PLGA**共聚物的轻松连接，然后以纳米颗粒的形式进行交联和纳米沉淀，从而制备基于PLGA的交联纳米颗粒。生产的纳米粒子将在生理条件下**测试其药物释放情况**，并将在体外研究期间评估其毒性。

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.