双重氧化还原敏感的生物可降解聚合物胶束的制备及表征  

Preparation and Characterization of Biodegradable Polymer With Dual-redox-response

作　　者：张学全 李赛[1] 张漫 万诗雨 ZHANG Xue-quan;LI Sai;ZHANG Man;WANG Shi-yu(College of Chemical Engineering,Sichuan University,Sichuan Chengdu 610065,China)

机构地区：[1]四川大学化学工程学院,四川成都610065

出　　处：《当代化工》2019年第11期2459-2463,共5页Contemporary Chemical Industry

摘　　要：以胱胺为引发剂,L-天冬氨酸4-苄酯内酸酐(BLA-NCA)和L-苯丙氨酸内酸酐(Phe-NCA)为单体通过开环聚合方法合成聚氨基酸共聚物(ASP(Z)),经氢溴酸脱保护得到侧链带羧基的氧化还原敏感响应的聚氨基酸共聚物(ASP-COOH),再将氧化还原敏感响应的喜树碱(CPT-SS-OH)小分子药物键合到聚合物侧链,得到双重氧化还原敏感响应的生物可降解两亲性聚合物,核磁共振氢谱(HNMR)和傅里叶红外光谱(FTIR)结果表明成功的合成了目标分子。通过两亲性高分子的自组装形成胶束,动态光散射(DLS)和扫描电子显微镜(SEM)对胶束的粒径及分布、zeta电位和微观形貌进行表征。结果发现,两亲性聚合物可形成球形结构胶束,粒径为(233.23±7.90)nm,zeta电位为(-21±1.10)m V。同时,胶束在生理条件下稳定,在谷胱甘肽(GSH)存在条件下,双重氧化还原敏感胶束结构"崩解"。设计的双重氧化还原敏感胶束可用于响应肿瘤的微环境而实现快速药物释放。The polyamino acid copolymers(ASP(Z)) were synthesized by ring-opening polymerization with cysteamine as initiator, L-Aspartic acid 4-benzyl ester NCA(BLA-NCA) and L-Phenylalanine NCA(Phe-NCA) as monomers. After deprotection with hydrobromic acid, a redox-sensitive copolymer with carboxyl groups(ASP-COOH) was obtained, and then the redox-sensitive response camptothecin(CPT-SS-OH) was bonded to the polymer side chain to obtain a dual-redox-sensitive biodegradable amphiphilic polymer. The results of 1 H NMR and FTIR showed that the target product was successfully synthesized. The micelles were formed by self-assembly of amphiphilic polymers, and the particle size and distribution, zeta potential and micromorphology of micelles were characterized by dynamic light scattering(DLS) and scanning electron microscopy(SEM). The results showed that the amphiphilic polymer can form spherical structural micelles with a particle size of(233.23±7.90)nm and a zeta potential of(-21±1.10)mV. At the same time, the micelles are stable under physiological conditions, and the double redox-sensitive micelle structure "disintegrated" in the presence of glutathione(GSH). Therefore, the dual-redox-sensitive micelles designed herein can be used to achieve rapid drug release under the tumor microenvironment.

关 键 词：双重氧化还原敏感 氨基酸 聚合物胶束 谷胱甘肽 

分 类 号：TQ460.1[化学工程—制药化工]