聚磷酸酯-紫杉醇前药合成及其还原响应药物释放研究  

Synthesis of amphiphilic polyphosphoester-PTX prodrug and its potential in reduction-responsive drug release

作　　者：陈旭东 付伟东 李锦锦 赵玲[1] 奚桢浩[1] CHEN Xudong;FU Weidong;LI Jinjin;ZHAO Ling;XI Zhenhao(China State Key Laboratory of Chemical Engineering,School of Chemical Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学化工学院,化学工程联合国家重点实验室,上海200237

出　　处：《化工学报》2024年第12期4815-4824,共10页CIESC Journal

基　　金：国家自然科学基金项目(21978089,22378116);化学工程联合国家重点实验室开放课题项目(SKL-ChE-21C04)。

摘　　要：用单甲氧基聚乙二醇(mPEG)大分子引发剂引发2-丁烯氧基-2-氧代-1,3,2-二氧磷杂环戊烷(BenEP)开环聚合制备了嵌段共聚物mPEG_(44)-b-PBenEP_(44),通过点击反应、酯化反应等聚合后改性方法,将二硫键与紫杉醇引入PBenEP链段的侧链,制备了一种还原响应性聚磷酸酯基紫杉醇前药mPEG_(44)-b-(PBenEP_(34)-gSS-PTX_(3))(PEBSP),其载药量为14.57%。PEBSP的自组装行为研究表明:PEBSP在水中能形成平均直径约为71 nm的球形纳米颗粒,其临界胶束浓度是60 mg·L^(-1);PEBSP球形纳米颗粒在正常条件下能稳定存在,在还原性介质中(10 mmol·L^(-1)谷胱甘肽)会因为二硫键断裂,可控、持续地释放药物紫杉醇。The block copolymer mPEG_(44)-b-PBenEP_(44) was prepared by the ring-opening polymerization of BenEP with monomethoxy polyethylene glycol(mPEG)as macroinitiator.A reduction-responsive polyphosphate-based paclitaxel prodrug mPEG_(44)-b-(PBenEP34-g-SS-PTX3)(PEBSP)was prepared by introducing the disulfide bond and paclitaxel into the pendant groups of PBenEP block,and the drug loading content(DLC)is 14.57%.The self-assembly behavior of PEBSP was studied by transmission electron microscopy(TEM),dynamic light scattering(DLS)and fluorescent analyses.The results show that PEBSP can form spherical particles with an average size of 71 nm in aqueous solution,and its critical micelle concentration is determined to be 60 mg∙L^(-1).PEBSP spherical nanoparticles can exist stably under normal conditions,and in a reducing medium(10 mmol·L^(-1) glutathione),the disulfide bond breaks and the drug paclitaxel is released in a controllable and continuous manner.

关 键 词：聚磷酸酯 前药 还原响应释放 聚合物 纳米材料 合成 

分 类 号：TQ323.9[化学工程—合成树脂塑料工业] TQ324.8