Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies  

作　　者：Yuequan Wang Cong Luo Shuang Zhou Xinhui Wang Xuanbo Zhang Shumeng Li Shenwu Zhang Shuo Wang Bingjun Sun Zhonggui He Jin Sun 

机构地区：[1]Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第5期643-652,共10页亚洲药物制剂科学（英文）

基　　金：funding from the National Natural Science Foundation of China(No.81703451 and 81773656);the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06);the Liaoning Revitalization Talents Program(No.XLYC1808017 and XLYC1907129);the China Postdoctoral Science Foundation(No.2020M670794);the Science and Technology Major Project of Liaoning(No.2019JH1/10300004)。

摘　　要：Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles(PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxelfatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cistrans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

关 键 词：DOCETAXEL Aliphatic prodrug Disulfide bond Self-assembly capacity In vivo drug delivery fate 

分 类 号：R943[医药卫生—药剂学]