The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies  

作　　者：Shuo Wang Tian Liu Yuetong Huang Chaoying Du Danping Wang Xiyan Wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun 

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China [3]School of Medical Devices,Shenyang Pharmaceutical University,Shenyang 110016,China [4]School of Pharmacy,Binzhou Medical University,Binzhou 256600,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第3期1400-1411,共12页药学学报（英文版）

基　　金：financially supported by National Key R&D Program of China(No.2022YFE0111600);National Natural Science Foundation of China(No.82272151 and 82204318);Doctoral Scientific Research Staring Foundation of Liaoning Province(No.2021-BS-130,China);General Program of Department of Education of Liaoning Province(No.LJKZ0953,China);Shenyang Young and Middle-aged Science and Technology Innovation Talents Support Program(RC220389,China)。

摘　　要：The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.

关 键 词：PRODRUGS NANOASSEMBLIES Self-assembly Branched-chain fatty alcohols Disulfide bond DOCETAXEL Efficacy Safety 

分 类 号：R96[医药卫生—药理学]