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Dually sensitive dextran-based micelles for methotrexate delivery

机译：基于甲氨蝶呤递送的基于甲般的葡聚糖的胶束

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摘要

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug.
机译：通过受控的自由基聚合从聚（N-异丙基丙烯酰胺）（PNIPAAM）（PNIPAAM）或聚乙二醇甲基醚（PEGMA）接枝的葡聚糖制备温度敏感的聚合物胶束，并评估为抗癌药物甲氨蝶呤（MTX）的递送系统。在将启动基团引入多糖骨架上后进行聚合物 - 嫁接，而不需要保护羟基并避免使用有毒溶剂。设计温度响应的葡聚糖共聚物以表现出自聚集行为，对MTX和高细胞内化的亲和力。此外，一些接枝聚合物掺入甲基丙烯酸2-氨基乙酯，通过离子相互作用加强胶束中的MTX包封。基于葡聚糖的胶束是细胞蛋白的，并且具有适当的尺寸以用作药物载体。 MTX释放依赖于pH和温度。聚（2-氨基乙基甲基丙烯酸甲酯）和肺腺苷与葡聚糖主链的组合允许在正常生理温度下完全释放MTX。通过肿瘤细胞（CHO-K1）高度内化的共聚聚合物胶束，与MTX一起加载时，与游离药物相比，导致细胞毒性增强。

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  • 来源
    《RSC Advances》 |2017年第24期|共13页
  • 作者

    Blanco-Fernandez B.; Concheiro A.; Makwana H.; Fernandez-Trillo F.; Alexander C.; Alvarez-Lorenzo C.;

  • 作者单位

    Univ Santiago de Compostela Fac Farm DPharma Grp GI 1645 R Dept Farm &

    Tecnol Farmaceut Santiago De Compostela 15782 Spain;

    Univ Santiago de Compostela Fac Farm DPharma Grp GI 1645 R Dept Farm &

    Tecnol Farmaceut Santiago De Compostela 15782 Spain;

    Univ Nottingham Sch Pharm Univ Pk Boots Sci Bldg Nottingham NG7 2RD England;

    Univ Nottingham Sch Pharm Univ Pk Boots Sci Bldg Nottingham NG7 2RD England;

    Univ Nottingham Sch Pharm Univ Pk Boots Sci Bldg Nottingham NG7 2RD England;

    Univ Santiago de Compostela Fac Farm DPharma Grp GI 1645 R Dept Farm &

    Tecnol Farmaceut Santiago De Compostela 15782 Spain;

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  • 正文语种 eng
  • 中图分类 化学;
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