Folic acid-functionalized drug delivery platform of resveratrol based on Pluronic 127/D-α-tocopheryl polyethylene glycol 1000 succinate mixed micelles.
Folic acid-functionalized drug delivery platform of resveratrol based on Pluronic 127/D-α-tocopheryl polyethylene glycol 1000 succinate mixed micelles.
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DOI：
10.2147/ijn.s130094
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发表时间：
2017
影响因子：
8
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Hao J;Tong T;Jin K;Zhuang Q;Han T;Bi Y;Wang J;Wang X
基于Pluronic 127 (P127)/D-α-生育酚聚乙二醇1000丁二酸酯（TPGS）混合胶束，构建叶酸功能化药物载体平台，有效递送模型药物白藜芦醇，以解决白藜芦醇水溶性差、代谢快的问题，并改善其在肿瘤部位的靶向蓄积。采用薄膜水化法制备了fa修饰的混合胶束，并采用中心复合设计方法对其进行了优化。并对胶束的大小、形态、包封效率和体外释放特性进行了表征。此外，我们在叶酸受体过表达的MCF-7细胞系中评估了胶束的细胞毒性和细胞摄取。还进行了体内药代动力学和生物分布研究。胶束平均粒径为~20 nm，呈球形，包封效率高达99.67%。荧光显微镜结果证实了fa共轭胶束在MCF-7细胞中的靶向能力。与溶液相比，fa修饰胶束表现出更好的药代动力学。此外，白藜芦醇负载FA胶束制剂在心脏和肾脏中的低积累避免了这些重要器官的毒性。由此可见，叶酸修饰的P127/TPGS混合胶束可能作为白藜芦醇的潜在递送平台。
A folic acid (FA)-functionalized drug vehicle platform based on Pluronic 127 (P127)/D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles was orchestrated for an effective delivery of the model drug resveratrol in order to address the problem of poor water solubility and rapid metabolism of resveratrol and improve its targeted accumulation at tumor site. The FA-decorated mixed micelles were prepared using thin-film hydration method and optimized by central composite design approach. The micelles were also characterized in terms of size and morphology, drug entrapment efficiency and in vitro release profile. In addition, the cytotoxicity and cell uptake of the micelles were evaluated in folate receptor-overexpressing MCF-7 cell line. In vivo pharmacokinetic and biodistribution studies were also performed. The average size of the micelles was ~20 nm with a spherical shape and high encapsulation efficiency (99.67%). The results of fluorescence microscopy confirmed the targeting capability of FA-conjugated micelles in MCF-7 cells. FA-modified micelles exhibited superior pharmacokinetics in comparison with that of solution. Further, the low accumulation of resveratrol-loaded FA micelles formulation in the heart and kidney avoided toxicity of these vital organs. It could be concluded that folate-modified P127/TPGS mixed micelles might serve as a potential delivery platform for resveratrol.