Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation

被引：55
作者：
Chen, Yanzuo [1 ,2 ]
Sha, Xianyi [1 ,2 ]
Zhang, Wei [1 ,2 ,3 ]
Zhong, Weitong [1 ,2 ]
Fan, Zhuoyang [1 ,2 ]
Ren, Qiuyue [1 ,2 ]
Chen, Liangcen [1 ,2 ]
Fang, Xiaoling [1 ,2 ]
机构：
[1] Fudan Univ, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
[2] Fudan Univ, PLA, Dept Pharmaceut, Sch Pharm, Shanghai 201203, Peoples R China
[3] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2013年 / 8卷
关键词：
multidrug resistance; drug delivery system; micelles; Pluronic; methotrexate; OVARIAN-CARCINOMA CELLS; BLOCK-COPOLYMERS; POLYMERIC MICELLES; DRUG-DELIVERY; P-GLYCOPROTEIN; BREAST-CANCER; BOUND DOXORUBICIN; TUMOR-CELLS; ANTICANCER; NANOPARTICLES;
D O I：
10.2147/IJN.S42368
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
A Pluronic polymeric mixed micelle delivery system was developed in this study by using Pluronic P105 and F127 block copolymers to encapsulate the antitumor compound, methotrexate (MTX). The MTX-loaded Pluronic P105/F127 mixed micelle exhibited the spherical shape with about 22 nm in diameter, high encapsulation efficiency (about 85%) and pH-dependent in vitro drug release. In this study, A-549 and KBv cell lines were selected as multidrug resistance tumor cell models, while H-460 and KB cell lines were chosen as sensitive tumor cells. The MTX-loaded Pluronic P105/F127 mixed micelle exhibited significant higher in vitro cytotoxicity in multidrug resistant tumor cells than that of control (MTX injection) mainly because of higher cellular uptake of MTX. The pharmacokinetic studies indicated that the Pluronic micelles significantly prolonged systemic circulation time of MTX compared to MTX injection. Moreover, a much stronger antitumor efficacy in KBv tumor xenografts nude mice was observed in the MTX-loaded Pluronic P105/F127 mixed micelle group, than MTX. Collectively, Pluronic P105/F127 mixed micelles could significantly enhance the antitumor activity of MTX and might be a promising drug delivery platform for multidrug resistance modulation.
引用
收藏
页码：1463 / 1476
页数：14
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