不同内核结构PEG-b-PCL胶束的制备及其载药性能的研究  

Preparation and Drug Delivery of PEG-b-PCL Micelles with Different Core Structures

作　　者：肖艳[1] 陈洋[1] 严金良[1] 郎美东[1] 

机构地区：[1]华东理工大学材料科学与工程学院超细材料制备与应用教育部重点实验室,上海200237

出　　处：《高分子学报》2015年第5期524-534,共11页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号51103041);教育部留学回国人员科研启动基金(第43批);中央高校基本科研业务费专项资金(项目号WD1414007);上海市"科技创新行动计划"国际合作项目(项目号14520720600)资助

摘　　要：以聚乙二醇单甲醚作大分子引发剂,异辛酸亚锡作催化剂,将不同比例的ε-己内酯(CL)与4-甲基-ε-己内酯(MCL)单体开环共聚,并通过控制CL和MCL的投料比以及投料方式,得到了疏水链段上CL和MCL不同比例和分布的4组聚合物.核磁和凝胶渗透色谱法表征了聚合物的结构,示差扫描量热法,广角X射线衍射和红外光谱表征了聚合物的结晶性.采用透析的方法,制备了4种聚合物的纳米胶束,以及载药(阿霉素DOX)胶束,并研究了胶束的自组装行为以及对阿霉素的包裹和释放情况.结果表明MCL单体的引入降低了聚合物的结晶性,提高了对DOX的载药量,加快了DOX的释放.通过激光共聚焦显微镜和流式细胞仪研究了Hep G2肝癌细胞对不同内核结构载药胶束的内吞情况,并用MTT法考察了胶束对细胞的毒害作用,细胞实验发现,Hep G2细胞对载DOX胶束的内吞以及载DOX胶束对细胞的杀伤能力和胶束内核的结构相关.Using stannous octoate （Sn（Oct）2） as catalyst and monomethoxy-poly（ethylene glycol） （mPEG） as macroinitiator,ε-caprolactone （CL） and y-methyl-ε-caprolactone （MCL） with different feed ratios were copolymerized by ring opening polymerization. By controlling the feed ratio and sequence of CL and MCL,four types of copolymers containing various hydrophobic CL/MCL ratio and distribution were obtained. 1H-NMR and GPC were used to characterize the structures of these four copolymers. DSC,WAXD and FTIR were applied to investigate their crystallinity. By dialysis method, four types of polymeric micelles and drug-loaded （ doxorubicin DOX） micelles were prepared and their self-assembly behavior was carefully studied. The loading and release profiles of DOX were also illustrated. The results indicated that the introduction of MCL decreased the crystallinity of copolymers, which led to the improvement in drug loading capacity and release speed. Confocal laser microscopy and flow cytometry were used to expose the endocytosis behavior of drug-loaded miceUes with different core structures taken by HepG2 hepatoma carcinoma cells. The cytotoxicity of micelles was then examined by MTT. All the cell experiments revealed that both endocytosis of DOX-loaded micelles taken by HepG2 and toxic effects of DOX-loaded micelles on cells were mainly influenced by the core structure of micelles.

关 键 词：聚己内酯 纳米胶束 自组装 药物控释 

分 类 号：TQ460.1[化学工程—制药化工]