Enhanced antitumor efficacy by methotrexate conjugated Pluronic mixed micelles against KBv multidrug resistant cancer

被引:60
作者
Chen, Yanzuo [1 ,2 ]
Zhang, Wei [1 ,2 ,3 ]
Gu, Jijin [1 ,2 ]
Ren, Qiuyue [1 ,2 ]
Fan, Zhuoyang [1 ,2 ]
Zhong, Weitong [1 ,2 ]
Fang, Xiaoling [1 ,2 ]
Sha, Xianyi [1 ,2 ]
机构
[1] Fudan Univ, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China
[2] Fudan Univ, PLA, Sch Pharm, Shanghai 201203, Peoples R China
[3] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA
基金
中国国家自然科学基金;
关键词
Methotrexate; Mixed micelles; Multidrug resistant; Drug delivery; Pluronic block copolymer; BLOCK-COPOLYMERS; DRUG-DELIVERY; POLYMERIC MICELLES; DOXORUBICIN; INHIBITION; CELLS; NANOPARTICLES; APOPTOSIS; REDUCTASE; ACID;
D O I
10.1016/j.ijpharm.2013.05.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A methotrexate (MTX) conjugated polymeric mixed micelles for MDR cancer therapy was developed in this study. To the best of our knowledge, MTX was firstly reported to be conjugated with Pluronic P105 (P105-MTX). The Pluronic F127 and P105-MTX polymeric mixed micelles (F127/P105-MTX) were fabricated by thin-film hydration technique, and performed superiority over physically entrapped MTX mixed micelles in drug loading capacity. The drug loading of MTX in F127/P105-MTX was found to be 3.42-fold higher than that of physically entrapped MTX mixed micelles. By conjugated to Pluronic, the amount of MTX in mixed micelles was increased 3.42-fold. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also demonstrated that F127/P105-MTX had better antitumor efficacy in KBv MDR cells compared to that of physically entrapped mixed micelles. In comparison with MTX injection, F127/P105-MTX can significantly enhance blood circulation time of MTX in rats. Moreover, a much stronger antitumor efficacy in KBv xenografts mice was observed in F127/P105-MTX group than that of MTX. Therefore, MTX-conjugated mixed micelles might be an effective platform for delivering chemotherapeutic agents to MDR tumors. (C) 2013 Elsevier B. V. All rights reserved.
引用
收藏
页码:421 / 433
页数:13
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