Redox-Responsive Molecular Gels Based on Camptothecin Prodrug with Disulfide Linkage for Controlled and Sustained Drug Release  

作　　者：CHANG Xiupeng LI Youmei CHEN Shu HE Feng ZHUO Renxi 

机构地区：[1]College of Chemistry and Molecular Science,Wuhan University,Wuhan 430072,Hubei,China

出　　处：《Wuhan University Journal of Natural Sciences》2017年第5期411-419,共9页武汉大学学报（自然科学英文版）

基　　金：Supported by the Natural Science Foundation of Hubei Province of China(2014CFB696);the Opening Project of Key Laboratory of Biomedical Polymers of Ministry of Education at Wuhan University(20150102);the National Natural Science Foundation of China(21074098)

摘　　要：A novel camptothecin （CPT） prodrug was successfully synthesized by conjugating CPT to adamantanecarboxylic acid （AD） via a cleavable disulfide linkage. The resulting CPT-ss-AD prodrug could act as a low molecular weight gelator to form molecular gels in water/water-miscible organic solvent mixture. Meanwhile, biode- gradable amphiphilic block copolymer mPEG-b-P （MAC-co-DTC） （PPMD） was also employed as an organic framework together with CPT-ss-AD to form gel structure. CPT-ss-AD/PPMD gel exhibited less compact molecular arrangement but much more stability than CPT-ss-AD gel. The two kinds of gels could effectively release the original CPT under reductive condition at a near-constant rate without any initial burst. As compared to CPT-ss-AD single-component gel, the two-component gel, CPT-ss-AD/PPMD, had a significantly higher release rate of CPT, while 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assays also indicated highly potent cytotoxic activity against HeLa cells.A novel camptothecin （CPT） prodrug was successfully synthesized by conjugating CPT to adamantanecarboxylic acid （AD） via a cleavable disulfide linkage. The resulting CPT-ss-AD prodrug could act as a low molecular weight gelator to form molecular gels in water/water-miscible organic solvent mixture. Meanwhile, biode- gradable amphiphilic block copolymer mPEG-b-P （MAC-co-DTC） （PPMD） was also employed as an organic framework together with CPT-ss-AD to form gel structure. CPT-ss-AD/PPMD gel exhibited less compact molecular arrangement but much more stability than CPT-ss-AD gel. The two kinds of gels could effectively release the original CPT under reductive condition at a near-constant rate without any initial burst. As compared to CPT-ss-AD single-component gel, the two-component gel, CPT-ss-AD/PPMD, had a significantly higher release rate of CPT, while 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assays also indicated highly potent cytotoxic activity against HeLa cells.

关 键 词：delivery PRODRUG molecular gels self-assembly POLYCARBONATES 

分 类 号：N0[自然科学总论—科学技术哲学]