pH 敏感聚合物胶束mPEG-GDE-OE的制备及其载药性能  

Preparation and Drug Delivery of pH-Sensitive Polymeric Micelles mPEG-GDE-OE

作　　者：孙慧 王菲 汪云云 巩凯 SUN Hui;WANG Fei;WANG Yunyun;GONG Kai(School of Parmaceutical Sciences,Jiangnan University,Wuxi 214122,Jiangsu,China)

机构地区：[1]江南大学药学院,江苏无锡214122

出　　处：《功能高分子学报》2020年第6期570-579,共10页Journal of Functional Polymers

基　　金：国家自然科学基金(51303069);中央高校基本科研业务费专项资金(JUSRP21940)。

摘　　要：以3-氨基-1,2-丙二醇为原料,合成了具有pH敏感性的原酸酯单体(2-十八烷氧基-1,3-二氧戊烷-4基)甲胺(OE),与单体甲氧基聚乙二醇胺(mPEG-NH2)、乙二醇二缩水甘油醚(GDE)经开环聚合(ROP)反应合成了pH敏感聚合物mPEG-GDE-OE,并以十八烷基胺(OA)为原料合成了非pH敏感聚合物mPEG-GDE-OA。采用溶剂挥发法制备了相应的聚合物胶束,并以阿霉素(DOX)为模型药物制备了相应的载药聚合物胶束。采用核磁共振氢谱(1H-NMR)对聚合物结构进行表征;利用动态光散射(DLS)仪表征胶束大小及粒径分布,用透射电镜(TEM)观察胶束形貌;采用动态透析法考察了胶束的体外药物释放性能;以人乳腺癌细胞(MCF-7)和宫颈癌细胞(Hela)为细胞模型,考察了载药聚合物胶束的细胞毒性与体外抗肿瘤活性。结果表明,mPEG-GDE-OE胶束和mPEG-GDE-OA胶束的粒径分别为(168.2±4.6)nm、(157.5±3.4)nm。载药聚合物胶束DOX/mPEG-GDE-OE和DOX/mPEG-GDE-OA的粒径比聚合物胶束的粒径略大,分别为(191.6±6.7)nm、(182.8±5.2)nm。与mPEG-GDE-OA胶束相比,mPEG-GDE-OE胶束具有良好的pH敏感性,表现出良好的控释性能和较强的肿瘤杀伤能力。An orthoester monomer of(2-(octadecyloxy)-1,3-dioxolan-4-yl)methanamine(OE)was synthesized using 3-amino-1,2-propanediol as starting material.A novel pH-sensitive polymer,mPEG-GDE-OE,was prepared by ring opening polymerization of OE,methoxypolyethylene glycol amine(mPEG-NH2)and glycol diglycidyl ether(GDE).The pHinsensitive polymer,mPEG-GDE-OA,was synthesized as a reference polymer.Amphiphilic polymers(mPEG-GDE-OE and mPEG-GDE-OA)could self-assemble into micelles by solvent volatilization method.Then doxorubicin(DOX)was used as a model drug to incorporate into mPEG-GDE-OE and mPEG-GDE-OA micelles.These polymers were characterized by 1HNMR.The size and the morphologies of the micelles were characterized by dynamic light scattering(DLS)and transmission electron microscopy(TEM).The drug release properties of micelles were investigated in vitro.Human breast cancer cells(MCF-7)and cervical cancer cells(Hela)were used as model tumor cell lines to investigate the cytotoxicity and antitumor activity of drug loaded polymer micelles in vitro.Results show that the particle sizes of mPEG-GDE-OE and mPEG-GDEOA micelles are(168.2±4.6)nm and(157.5±3.4)nm,respectively.The particle sizes of drug-loaded micelles,DOX/mPEGGDE-OE and DOX/mPEG-GDE-OA,are(191.6±6.7)nm and(182.8±5.2)nm,respectively.Compared with mPEG-GDE-OA micelles,mPEG-GDE-OE micelles have good pH sensitivity,good controlled release performance and strong tumor killing ability.

关 键 词：PH敏感 开环聚合 聚合物 胶束 药物载体 

分 类 号：R94[医药卫生—药剂学]