两亲性杂臂星型嵌段共聚物胶束的制备、表征及载药性能研究  

Preparation,characterization and drug-loading capacity of amphiphilic mikto-arm star block copolymer micelles

作　　者：李志年[1] 林娟[2] 李立冬[1] 周庆翰[1] 

机构地区：[1]西南民族大学化学与环境保护工程学院,四川成都610041 [2]成都医学院生物医学系,四川成都610083

出　　处：《化学研究与应用》2015年第6期858-864,共7页Chemical Research and Application

基　　金：国家自然科学青年基金项目(21404086)资助;四川省教育厅基金(14ZB0406;10ZC091)资助;西南民族大学研究生学位点建设项目(2015XWD-S0703)资助

摘　　要：以溴代异丁酰溴与3,5-二羟基苯甲酸制备3,5-二(2-溴-2丙酰氧基)苯甲酸,再与聚乙二醇单甲醚酯化,合成含溴大分子引发剂PEG-Br2。以苯乙烯为单体,利用原子转移自由基聚合方法(ATRP)合成了两种不同亲疏水段比例的两亲性星型杂臂嵌段共聚物PEG-b-(PS)2。本实验利用FTIR、1H-NMR、GPC等技术对聚合物的分子结构及分子量进行表征,利用透析法制备聚合物胶束;采用AFM对聚合物胶束的纳米结构进行观察;采用荧光探针法测得其临界胶束浓度(CMC)分别为0.99 mg·L-1和0.59 mg·L-1;利用DLS测得聚合物胶束粒径为150 nm左右;以疏水型抗肿瘤药物氨甲喋呤(MTX)为模型药物,对载药胶束的体外释药行为进行了研究,测得聚合物胶束的载药量分别为为13.32%和10.00%,包封率分别为61.75%和46.82%。结果表明,随着疏水段的增大,星型杂臂嵌段共聚物胶束药物包载量及CMC随之降低,且在人体pH条件下药物释放较低;同时发现两种载药胶束在肿瘤细胞酸性条件下释药速率增加。综上,此类结构的聚合物胶束作为抗肿瘤药物MTX的载体分子具有很好的应用前景。3,5-bis（2-bromo-2-methylpropanoyloxy） benzoic acid was synthesized with 2-bromo-2-methylpropanoyl bromide and 3,5-dihydroxy benzoic acid,followed by the esterification with polyethylene glycol monomerthyl ether to prepare the macroinitiator.Two amphiphilic mikto-arm star block polymers,PEG-b-（PS）2,were polymerized by atom transfer radical polymerization（ATRP） with different hydrophlic/hydrophobic segments ratio.The chemical structure and molecular weight of the star copolymers were characterized by FTIR,1H-NMR,and GPC.The polymeric micelles were prepared by dialysis,and AFM was used to observe the nano-structure of the polymeric micelles.The critical micelle concentrations of two polymeric micelles were 0.99 and 0.59 mg·L-1,which were measured by fluorescence probe technology.DLS was utilized to measure the mean diameter of the drug loaded polymer micelles（about 150 nm）.To study the potential application of the copolymer micelle as drug carrier,methotrexate（MTX） was utilized as hydrophobic model drug.The drug loading were 13.32% and 10.00%,and encapsulation efficiency were 61.75%and 46.82% respectively.The in vitro MTX release experiments indicated that the drug-loaded micelles have a rapid release at acid pH.Generally,the experimental results indicated that with increase of hydrophobic segment the CMC and drug loading capacity of mikto-arm star block copolymer micelles decreased,and a lower release amount was observed at pH = 7.4.Therefore,the polymer micelles may be a potential drug carrier in delivery system for MTX.

关 键 词：PEG-b-(PS)2 聚合物胶束 MTX 药物载体 

分 类 号：O632.13[理学—高分子化学]