叶酸介导的聚乙二醇-聚苹果酸-喜树碱聚合物前药的制备和性质初探  

Polymeric prodrug of folate-mediated poly(ethylene glycol)-poly(malic acid)-camptothecin:preparation,characterization and biological evaluation

作　　者：李伟[1] 段晓[1] 范黎[1] 乔友备[1] 吴红[1] 

机构地区：[1]第四军医大学药学院药物化学与药物分析教研室,西安710032

出　　处：《西北药学杂志》2013年第4期396-399,共4页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:30970788;81271687)

摘　　要：目的合成生物基大分子聚苹果酸(PMLA),制备叶酸介导的喜树碱-聚苹果酸聚合物前药FA-PEG-PMLA-CPT,研究其体外释药特性和细胞毒性。方法以L-天冬氨酸为原料合成PMLA,将(FA-)PEG、CPT分别以酰胺键、酯键连接到PMLA骨架上,制备得到聚合物前药FA-PEG-PMLA-CPT。红外光谱、核磁共振光谱表征PMLA及聚合物药物的结构,动态透析法模拟体外释药特性,采用Hela细胞研究聚合物药物体系的内摄作用和细胞毒性。结果成功制备了药物载体PMLA和聚合物前药FA-PEG-PMLA-CPT;FA-PEG-PMLA-CPT具有一定的缓释性,但是无明显的pH值响应特性;FA-PEG-PMLA-CPT有效地提高了CPT的细胞内摄作用,细胞毒性明显高于CPT。结论聚合物前药FA-PEG-PMLA-CPT是一种潜在的靶向性给药体系。Objective The biomacromolecule of poly malic acid （PMLA） was synthesized to prepare a novel folate acid-decorated poly （ethylene glyeol）-poly （malie acid）-eamptotheein （F^PEG-PMLA-CPT） polymeric coniugate （FA-PEG-PMLA-CPT） for active tumor targeting. Methods The structure of the polymeric prodrug was confirmed by 1 H-NMR. Furthermore,the conjugation effi- ciency and drug release property were determined. The cellular uptake and cytotoxicity were assessed by using human cervical cancer Hela cells in vitro cell model. Results PMLA and FA-PECrPMLA CPT were successfully prepared. The polymeric pro- drug had a favourable drug release property which was independent of pH. FA-PEG-PMLA-CPT effectively enhanced the cellular uptake of CPT and in vitro cytotoxicity. Conclusion FA-PEG-PMLA-CPT conjugate could be used as a promising CPT carrier for its targeted and intracellular delivery.

关 键 词：聚合物前药 喜树碱 叶酸 主动靶向 

分 类 号：R944[医药卫生—药剂学]