Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation.
Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation.
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DOI：
10.2147/ijn.s42368
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发表时间：
2013
影响因子：
8
通讯作者：
Fang X
中科院分区：
文献类型：
--
作者：
Chen Y;Sha X;Zhang W;Zhong W;Fan Z;Ren Q;Chen L;Fang X
以Pluronic P105和F127嵌段共聚物为载体，制备了一种用于包裹抗肿瘤药物甲氨蝶呤（MTX）的Pluronic聚合物混合胶束给药系统。载MTX的Pluronic P105/F127混合胶束呈球形，粒径约22 nm，包封率约85%，体外释药具有pH依赖性。本研究选择A-549和KBv细胞作为多药耐药肿瘤细胞模型，H-460和KB细胞作为敏感肿瘤细胞模型。载MTX的Pluronic P105/F127混合胶束对多药耐药肿瘤细胞的体外细胞毒作用显著高于对照组（MTX注射液），主要是因为细胞对MTX的摄取增加。药物动力学研究表明，与MTX注射液相比，Pluronic胶束可显著延长MTX的体循环时间。此外，在KBv肿瘤异种移植裸鼠中，在载MTX的Pluronic P105/F127混合胶束组中观察到比MTX强得多的抗肿瘤效力。Pluronic P105/F127混合胶束可显著增强MTX的抗肿瘤活性，有望成为一种新型的抗多药耐药药物载体。
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.