文献类型：期刊文献

英文题名：Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery

作者：Qi, Dingqing[1];Gong, Feirong[1];Teng, Xin[1];Ma, Mingming[1];Wen, Huijing[1];Yuan, Weihao[1];Cheng, Yi[1];Lu, Chong[1]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai, Peoples R China

年份：2017

卷号：28

期号：14

起止页码：1538

外文期刊名：JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION

收录：;EI(收录号：20172303727600);WOS:【SCI-EXPANDED(收录号:WOS:000406503300008)】；

基金：This work was supported by the National Science and Technology Major Projects of China for Major New Drugs Innovation and Development [grant number 2014ZX09301306-006].

语种：英文

外文关键词：Micelle; 9-Fluorenylmethoxycarbonyl; drug-interactive; docetaxel; drug delivery

摘要：Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB)(2)) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB)(2) was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (similar to 17-19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB)(2) micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB)(2) micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.