触发式自释放喜树碱聚合物前药的合成与释放调控  

Self-immolative camptothecin polymeric prodrugs for controlled drug release

作　　者：白皓宇 周珠贤[1] 申有青[1] BAI Hao-yu;ZHOU Zhu-xian;SHEN You-qing(Zhejiang Key Laboratory of Smart Biomaterials,College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China)

机构地区：[1]浙江大学化学工程与生物工程学院,浙江省智能生物材料重点实验室,浙江杭州310027

出　　处：《高校化学工程学报》2022年第4期570-578,共9页Journal of Chemical Engineering of Chinese Universities

基　　金：国家重点研发计划(2021YFA1201200);国家自然科学基金(52073249,21875211)。

摘　　要：精准控制药物释放是提高药物疗效并降低毒副作用的关键。触发式自释放系统可用于药物的程控和定点释放。研究构建一种触发式自释放的喜树碱(CPT)聚合物前药平台。通过开环易位聚合,合成一系列分子质量相近但氨基链长短/数量不同的聚合物前药(PEG_(n)-E_(m)-CPT_(2)和PEG_(n)-D_(m)-CPT_(2)),重点探究氨基链长短/数量对CPT自释放的影响。结果表明,氨基链长短、数量和pH均可以改变CPT的释放行为。通过控制氨基数量,PEG_(n)-E_(m)-CPT_(2)和PEG_(n)-D_(m)-CPT_(2)在180 h的释放量可分别从10%调控至89%或62%。此外,利用酸敏感性β-羧酸酰胺修饰氨基可实现酸触发CPT释放。该研究报道了利用邻近侧链氨基催化分子内水解现象来调控药物的释放性能。Precise controlling of drug release profiles is essential for enhancing drug efficiency and reducing side effects.Self-immolative systems have been developed as promising platforms for programmable and on-demand drug release.A self-immolative camptothecin(CPT)-based polymeric prodrugs for controlled drug release was constructed.The polymeric CPT prodrugs were prepared by Grubbs 3 catalyzed(3rd generation)ring-opening metathesis polymerization(ROMP).The results show that neighboring amine groups in the polymeric prodrugs can catalyze the hydrolysis of CPT ester and promote CPT release.The drug release profile of CPT was tunable by pH,amine chain length and amine numbers.The drug release of PEG_(n)-E_(m)-CPT_(2) and PEG_(n)-D_(m)-CPT_(2) can be tuned from 10% to 89% and 62% within 180 hours,respectively.By amidization of amine groups with acid-responsive β-carboxylic amides,polymeric CPT prodrugs with acid-responsive drug release was obtained.This work demonstrates the neighboring amine catalyzed hydrolysis can be used for self-immolative drug release.

关 键 词：触发式自释放 聚合物前药 喜树碱 释放调控 

分 类 号：R979.1[医药卫生—药品]