文献类型：期刊文献

英文题名：Drug-interactive mPEG-b-PLA-Phe(Boc) micelles enhance the tolerance and anti-tumor efficacy of docetaxel

作者：Gong, Feirong[1];Wang, Rongrong[1];Zhu, Zhengquan[1];Duan, Jiayao[1];Teng, Xin[1];Cui, Zhong-Kai[2,3,4]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Minist Educ, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China;[2]Southern Med Univ, Sch Basic Med Sci, Dept Cell Biol, Guangzhou 510515, Peoples R China;[3]Southern Med Univ, Affiliated Hosp 3, Dept Otorhinolaryngol, Guangzhou, Peoples R China;[4]Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou, Peoples R China

年份：2020

卷号：27

期号：1

起止页码：238

外文期刊名：DRUG DELIVERY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000510322700001)】；

基金：This work was supported by research grant from the Key Research & Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110104002], National Natural Science Foundation of China [31800840] and Starting grant of Southern Medical University [G618289090].

语种：英文

外文关键词：Polymeric micelles; docetaxel; anti-tumor efficacy

摘要：Docetaxel (DTX) is one of the most promising chemotherapeutic agents for a variety of solid tumors. However, the clinical efficacy of the marketed formulation, Taxotere (R), is limited due to its poor aqueous solubility, side effects caused by the emulsifier, and low selective DTX distribution in vivo. Here a facile, well-defined, and easy-to-scale up DTX-loaded N-(tert-butoxycarbonyl)-(L)-phenylalanine end-capped methoxy-poly(ethylene glycol)-block-poly((D,L)-lactide) (mPEG-b-PLA-Phe(Boc)) micelles (DTX-PMs) were prepared in an effort to develop a less toxic and more efficacious docetaxel formulation. The physicochemical properties, pharmacokinetics, biodistribution, and in vivo anti-tumor efficacy were evaluated in comparison to the marketed DTX formulation Taxotere (R). DTX was successfully encapsulated in the hydrophobic micellar core with a high encapsulation efficiency (> 95%) and a high drug loading capacity (4.81 +/- 0.08%). DTX-PMs exhibited outstanding stability in the aqueous environment due to the strong interactions between the terminal amino acid residues and docetaxel. The pharmacokinetic study in Sprague-Dawley rats revealed higher DTX concentrations in both whole blood and plasma for the group treated with DTX-PMs than that treated with Taxotere (R) due to the improved stability of the micellar formulation. In human non-small cell lung cancer (A549) tumor-bearing Balb/c nude mice, DTX-PMs significantly improved DTX accumulation and stalled DTX elimination in tumors than in bone marrow. Furthermore, only by half of the DTX dosage, our DTX/mPEG-b-PLA-Phe(Boc) micelles can achieve similar therapeutic effects as Taxotere (R). Altogether, DTX-PMs hold great promise as a simple and effective drug delivery system for cancer chemotherapy.