Multifunctional Pluronic P123/F127 mixed polymeric micelles loaded with paclitaxel for the treatment of multidrug resistant tumors
Multifunctional Pluronic P123/F127 mixed polymeric micelles loaded with paclitaxel for the treatment of multidrug resistant tumors
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负载紫杉醇的多功能Pluronic P123/F127混合聚合物胶束用于治疗多药耐药肿瘤
DOI：
10.1016/j.biomaterials.2010.12.039
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发表时间：
2011-04-01
期刊：
影响因子：
14
通讯作者：
Fang, Xiaoling
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Shi, Yuan;Fang, Xiaoling
本研究以紫杉醇（PTX）为模型药物，探讨叶酸通过叶酸受体介导的内吞作用发挥主动靶向作用，并结合Pluronic嵌段共聚物克服多药耐药（MDR）的可能性，以促进静脉给药后药物向MDR肿瘤的传递。首次制备了叶酸功能化的Pluronic P123/F127混合胶束（FPF-PTX），并以紫杉醇和紫杉醇为对照，进行了体内外实验。FPF-PTX粒径约20 nm，呈球形，包封率高。由于叶酸受体介导的内吞作用，发现FPF-PTX的细胞摄取高于PF-PTX。体外细胞毒性、细胞凋亡和细胞周期阻滞研究也表明FPF-PTX比PF-PTX和Taxol更有效。大鼠体内药代动力学研究表明，聚合物胶束显著提高紫杉醇的生物利用度（约3倍）。此外，在荷KBv MDR肿瘤异种移植物的BALB/c小鼠中，FPF-PTX组显示出更强的抗肿瘤效力，并且体内外具有良好的相关性。总之，叶酸偶联的Pluronic胶束可能是一种潜在的载体，用于将疏水性化疗药物递送至MDR肿瘤。皇冠版权所有（C）2010由爱思唯尔有限公司出版。保留所有权利。
The aim of this study was to exploit the possibility of combination of active targeting function of folic acid by folate receptor-mediated endocytosis and overcoming multidrug resistance (MDR) by Pluronic block copolymers to promote drug delivery to MDR tumor following intravenous administration with paclitaxel (PTX) as model drug. Folic acid functionalized Pluronic P123/F127 mixed micelles encapsulating PTX (FPF-PTX) was firstly developed and tested in vitro and in vivo, while PTX-loaded Pluronic P123/F127 mixed micelles (PF-PTX) and Taxol were used as control. FPF-PTX was about 20 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake of FPF-PTX was found to be higher than that of PF-PTX due to the folate receptor-mediated endocytosis effect. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that FPF-PTX was more potent than those of PF-PTX and Taxol. In vivo pharmacokinetic study in rats showed that the polymeric micelles significantly enhanced the bioavailability of PTX (similar to 3 fold) than Taxol. Moreover, in BALB/c mice bearing KBv MDR tumor xenografts, stronger antitumor efficacy was shown in FPF-PTX group, with good correlation between in vitro and in vivo. In conclusion, folate-conjugated Pluronic micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to MDR tumors. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.