用于盐酸阿霉素增敏的双给药水凝胶体系制备  

Preparation of hydrogel dual-drug delivery system for enhancing DOX·HCl efficacy

作　　者：刘鸿鑫 张强[3] 程昉[1,2] 董继程 刘波 朱娇慧[4] LIU Hongxin;ZHANG Qiang;CHENG Fang;DONG Jicheng;LIU Bo;ZHU Jiaohui(State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China;Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China;School of Bioengineering, Dalian University of Technology, Dalian 116024, China;Hubei Gedian Humanwell Pharmaceutical Co., Ltd, Ezhou 430206, China)

机构地区：[1]大连理工大学精细化工国家重点实验室,辽宁大连116024 [2]大连理工大学化工学院药学系,辽宁大连116024 [3]大连理工大学生物工程学院,辽宁大连116024 [4]湖北葛店人福药业有限责任公司,湖北鄂州430206

出　　处：《大连理工大学学报》2021年第4期337-343,共7页Journal of Dalian University of Technology

基　　金：国家自然科学基金资助项目(21773022);国家重点研发计划资助项目(2018YFA0703000);中央高校基本科研业务费专项资金资助项目(DUT20YG103).

摘　　要：多药耐药型乳腺癌细胞对抗癌药物盐酸阿霉素(DOX·HCl)敏感性下降,需要设计和制备一种实现抗癌药物增敏的给药体系.提出一种同时负载DOX·HCl和齐墩果酸(OA)的双给药聚乙二醇水凝胶体系.该体系基于具有亲水和疏水性的聚乙二醇水凝胶,实现DOX·HCl和OA的共包封和共释放.两种药物的释放通过氧-迈克尔加成反应和醇修饰来调节.结果表明双给药水凝胶体系具有杀伤多药耐药型乳腺癌细胞株(MCF/MDR)的协同作用,有助于新型给药体系的设计和多药耐药型乳腺癌治疗的临床实践.Doxorubicin hydrochloride(DOX·HCl),an anticancer drug,is becoming less effective toward multidrug-resistant breast cancer cells.Herein,a hydrogel dual-drug delivery system is proposed which can enhance DOX·HCl efficacy.This system is based on a polyethylene glycol hydrogel with both hydrophilic and hydrophobic domains,in order to realize co-encapsulation and co-release of DOX·HCl and oleanolic acid(OA).The release of the two drugs is adjusted by oxo-Michael addition reaction followed by alcohol modification.It is found that this hydrogel dual-drug delivery system exhibits synergistic effect of killing MCF/MDR cell line which resists anti-tumor drugs.The system sheds light upon designing new materials for drug delivery and solving problems in clinical treatment of multidrug-resistant breast cancer.

关 键 词：水凝胶 聚乙二醇 多药耐药型乳腺癌 耐药性恢复 双给药 

分 类 号：R914[医药卫生—药物化学]