氧化还原敏感型胶束的构建和药物控释性能  

Construction and Controlled Release Properties of Redox Responsive Micelles

作　　者：余丽丽[1] 刘乾 姚琳[1] 李立[1] 刘少静[1] 杨宽[1] 田洪玉 Lili Yu, Qian Liu, Lin Yao, Li Li, Shaojing Liu, Kuan Yang, Hongyu Tian(Department of Pharmacy, Xi ＇ an Medical University, Xi ＇ an 710021 , China)

机构地区：[1]西安医学院药学院,陕西西安710021

出　　处：《高分子材料科学与工程》2018年第9期20-25,共6页Polymer Materials Science & Engineering

基　　金：陕西省高校科协青年托举计划项目(20170410);西安医学院药学省级重点学科建设项目(2016YXXK03);西安医学院国家基金培育项目(2017GJFY07);西安医学院校级大学生创新创业项目(11111524047;11111524016);西安医学院省级重点学科-药学(1007);国家自然科学基金项目(81302706);陕西省科技厅自然科学基础研究计划项目(2018JQ8041;2017JM8124);陕西省大学生创新创业训练计划项目(1757;1649;2310;2309;2318)

摘　　要：采用3,3'-二硫代二丙酸、乙酰氯、N-Boc-乙醇胺、ε-己内酯、聚乙二醇单甲醚等为原料,通过分子内脱水、酰化、开环聚合、缩合等一系列反应制备了以聚乙二醇单甲醚(mPEG)为亲水端,聚己内酯(PCL)为疏水端,中间含有二硫键链接的两亲聚合物——mPEG-SS-PCL。通过核磁共振氢谱、傅里叶变换红外光谱对聚合物的结构进行表征;以阿霉素(DOX)为模型药物,探讨胶束载药性能和氧化还原敏感性能。并通过MTT法评价了聚合物的细胞毒性。研究结果表明,mPEGSS-PCL可自组装形成胶束,该胶束粒径分部均匀,外表圆整,粒径约为190 nm,其结构具有良好的氧化还原敏感性;胶束的载药量为10. 0%,载药稳定性良好,且具有显著的药物控制释放性;此外,胶束在细胞水平表现为良好的生物安全性。The redox responsive amphiphilic polymer which contains disulfide linkage between hydrophilic block （methoxypolyethylene glycol, mPEG） and hydrophobic block（polycaprolactone, PCL） was prepared through a series of reactions including intramolecular dehydration, acylation, ring opening polymerization, condensation reaction, using 3, 3＇-dithiodipropionic acid, acetyl chloride, 2-boc-ethanolamine, ε-caprolactone, polyethylene glycol monomethyl ether as raw materials. The structure of polymers was characterized by 1H-NMR and FT-IR. Package load capacityand glutathione （GSH） sensitive properties were studied using doxorubicin （DOX） as model drug. The particle size and zeta potential of the micelles were investigated by laser particle size analyzer. The cytotoxicity of micelleS was evaluated by MTT method. The results show that mPEG-SS-PCL can be self-assembled into micelles with uniform size,, rounded surface. The particle size of micelles is about 190 nm., and the structure of the micelles is redox dependent. DOX loading efficiency of micelles with remarkable drug loading stability is 10.0%. The drug release process can be controlled by GSH level. Furthermore, micelles show good biological safety at cell level.

关 键 词：氧化还原敏感 胶束 两亲聚合物 阿霉素 

分 类 号：O648.17[理学—物理化学]