文献类型：期刊文献

英文题名：A novel cabazitaxel-loaded polymeric micelle system with superior in vitro stability and long blood circulation time

作者：Han, Xiaoxiong[1,2];Chen, Dan[1,2];Sun, Jing[1,2];Zhou, Jinsong[4];Li, Duan[4];Gong, Feirong[3];Shen, Yaling[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Bio Technol, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[4]Shanghai Yizhong Biotech Co Ltd, Shanghai, Peoples R China

年份：2016

卷号：27

期号：7

起止页码：626

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

收录：;EI(收录号：20160902019706);WOS:【SCI-EXPANDED(收录号:WOS:000373015000006)】；

基金：This work was supported by Shanghai Leading Academic Discipline Project [Project B505]; National Special Fund for State Key Laboratory of Bioreactor Engineering [No. 2060204].

语种：英文

外文关键词：stability; polymeric micelle; blood circulation time; Cabazitaxel

摘要：Cabazitaxel (CTX) is a second-generation semisynthetic taxane that demonstrates antitumor activity superior to docetaxel. However, the low aqueous solubility of CTX has hampered its use as a therapeutic agent. In this work, CTX-loaded N-t-butoxycarbonyl-L-phenylalanine end-capped monomethyl poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PLA-Phe(Boc)/CTX) micelles were prepared to improve the solubility of CTX while retaining its superior stability before accessing the tumor site. The mPEG-PLA-Phe(Boc)/CTX micelles showed excellent stability in vitro compared with mPEG-PLA/CTX micelles. When stored at 25 degrees C, the mPEG-PLA/CTX micelles tended to aggregate within 1h, whereas the mPEG-PLA-Phe(Boc)/CTX micelles were uniformly transparent even after three weeks. Dilution of mPEG-PLA/CTX micelles widened their size distribution and decreased the encapsulation efficiency, while significant change was not found in mPEG-PLA-Phe(Boc)/CTX micelles, even when diluted 1000-fold. Pharmacokinetic results in Sprague-Dawley rats indicated that, compared with Jevtana((R)), intravenous administration of mPEG-PLA-Phe(Boc)/CTX micelles stably retained the CTX in plasma with 26.03-fold larger of the area under the time-concentration curve, 2.13-fold longer of the half-life, and 9.99-fold higher of the maximum concentration. In conclusion, mPEG-PLA-Phe(Boc) micelle may be a potential nanocarrier not only to improve the solubility of CTX but also to prolong the blood circulation time, which results in improved biological activity.