温度/pH响应性MPEG-b-PCL/PNVCL-b-PCL共聚物复合胶束的制备及载药性质  

Preparation and Drug Delivery Properties of Thermo/pH Dual Responsive Copolymer Composite Micelles of MPEG-b-PCL/PNVCL-b-PCL

作　　者：张萌 王绍森 辛宇豪 刘学 吴秋华[1] 张国林[1] ZHANG Meng;WANG Shaosen;XIN Yuhao;LIU Xue;WU Qiuhua;ZHANG Guolin(College of Chemistry,Liaoning University,Shenyang 110036,China)

机构地区：[1]辽宁大学化学院,沈阳110036

出　　处：《高等学校化学学报》2020年第12期2822-2831,共10页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:51373073);辽宁省自然科学基金(批准号:2019-ZD-0192,20180550947)资助.

摘　　要：以基于亚胺键的嵌段共聚物为构筑单元的温度/pH响应性共聚物复合胶束(CMs),由于具有亚胺键和核-壳-冠结构,表现出较高的灵敏度和稳定性.以聚乙二醇单甲醚(MPEG)、N-乙烯基己内酰胺(NVCL)和ε-己内酯(ε-CL)为原料,分别制备了端醛基聚乙二醇单甲醚(MPEG-CHO)、端醛基聚N-乙烯基己内酰胺(PNVCLCHO)和端氨基聚己内酯(H2N-PCL),利用希夫碱反应,进一步制备了基于亚胺键的聚乙二醇单甲醚-b-聚己内酯(MPEG-b-PCL)和聚N-乙烯基己内酰胺-b-聚己内酯(PNVCL-b-PCL)嵌段共聚物,对共聚物结构进行了确认.以MPEG-b-PCL和PNVCL-b-PCL为构筑单元,制备了共聚物复合胶束,研究了复合胶束对阿霉素的包载、释放性质和细胞毒性等.研究结果表明,室温下MPEG-b-PCL和PNVCL-b-PCL能够在水中自组装形成以PCL为核、MPEG和PNVCL为混合壳的共聚物复合胶束,在生理温度下,温敏性PNVCL链段发生相变塌缩在PCL核表面,能够防止药物扩散释放,亲水性MPEG链段形成可控通道.药物体外释放结果表明,在弱酸性环境中,亚胺键能够断裂,胶束被破坏,促进药物的释放,噻唑蓝(MTT)实验表明,复合胶束的细胞毒性较低.Thermo/pH dual responsive copolymer composite micelles(CMs)based on the block copolymers with imine bonds show higher sensitivity and stability due to their imine linkage and core-shell-crown three la-yer structure.Using polyethylene glycol monomethyl ether(MPEG),N-vinyl caprolactam(NVCL)andε-caprolactone(ε-CL)as raw materials,the aldehyde-terminated poly(ethylene glycol)monomethyl ether(MPEG-CHO),aldehyde-terminated poly(N-vinylcaprolactam)(PNVCL-CHO)and amino-terminated poly⁃caprolactone(H2N-PCL)were prepared respectively.Block copolymers,poly(ethylene glycol)monomethyl ether-b-poly(ε-caprolactone)(MPEG-b-PCL)and poly(N-vinylcaprolactam)-b-poly(ε-caprolactone)(PNVCL-b-PCL)based on imine bond,were synthesized by reaction of H2N-PCL with MPEG-CHO and PNVCL-CHO.At room temperature,MPEG-b-PCL and PNVCL-b-PCL self-assembled to form CMs with PCL as the core and MPEG/PNVCL as the mixed shell in water.At the physiological temperature,thermo-respon⁃sive PNVCL collapsed on the PCL core,while MPEG still stretched to form core-shell-corona micelles,which might protect the drug encapsulated in the core.Studies on the in vitro drug release showed that a much faster release rate was observed at slightly acidic media,due to the disruption of imine bonds.3-(4,5)-Dimethylthia⁃hiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay demonstrated the low cytotoxicity of the composite micelles.

关 键 词：温度/pH响应 亚胺键 共聚物复合胶束 载药 

分 类 号：O632.1[理学—高分子化学]