PEG-PLGA纳米粒长循环机制与载TNF-α拮抗肽性能研究.pdfVIP

PEG-PLGA 纳米粒长循环机制及载TNF-α拮抗肽性能研究 杨安树，杨林，刘卫*，李卓娅，杨祥良 （华中科技大学国家纳米药物工程技术研究中心，武汉 430074 ） 摘要：近年来，高分子纳米载药系统作为多肽、蛋白质药物载体展示了良好的临床应用 前景，成为药学领域的研究热点。但是，有关高分子纳米载药系统长循环机制的基础科学问 题尚待深入研究。本课题组采用开环聚合法合成了不同分子量的聚乙二醇-聚乳酸羟基乙酸 （PEG-PLGA ）两嵌段共聚物，通过自乳化溶剂扩散法（SESD ）制备了不同表面特性和粒 径 PEG-PLGA 纳米粒（PEG-PLGA-NPs ），较系统的研究了血清蛋白吸附、调理作用与 PEG-PLGA-NPs 表面 PEG 修饰、粒径之间的关系，巨噬细胞吞噬与 PEG-PLGA-NPs 表面 PEG 修饰、粒径以及血清蛋白吸附、调理作用之间的关系，以阐明高分子纳米载药系统长 循环机制。同时，制备了载TNF-α拮抗肽（TNF-BP ）的PEG-PLGA-NPs ，并对其载药性能、 体外药物释放行为和生物活性等进行了研究。本文对上述研究工作进行了综述。 关键词：聚乙二醇-聚乳酸羟基乙酸纳米粒（PEG-PLGA-NPs ）；TNF-α拮抗肽（TNF-BP ）； 长循环机制；血浆调理作用；巨噬细胞吞噬作用 Long-circulating Mechanism of PEG-PLGA Nanoparticles and the Properties of TNF-α Blocking Peptide Loaded Nanoparticles * Anshu Yang, Lin Yang, Wei Liu , Xiangliang Yang, Huibi Xu (National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China) Abstract: Recently, nano drug delivery systems (NDDS) that are made up of biodegradable materials have been the hotspot research in modern pharmacy. However, to date, some mechanisms involved in the long-circulating NDDS have not been fully understood. In this study, a series of methoxypolyethyleneglycol modified poly (D, L-lactide-co- glycolide) nanoparticles (PEG-PLGA-NPs) were prepared by the spontaneous emulsification solvent diffusion (SESD) method, and the correlations among the surface property and size of nanoparticles, opsonization by serum protein and phagocytic uptake were studied to illustrate the long-circulating mechanisms for PEG-PLGA-NPs. Tumor necrosis factor alpha blocking peptide (TNF-BP) was loaded on PEG-PLGA-NPs by electrostatic interaction, and TNF-BP loading capacity, bioactivity and the in vitro drug release were studied. Key words: PEG-modified poly(lactide-