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.
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机译：温度敏感的聚合物胶束是通过受控自由基聚合从接枝有聚（ N -异丙基丙烯酰胺）（PNIPAAm）或聚乙二醇甲基醚（PEGMA）的葡聚糖制备的，并评估其递送甲氨蝶呤（MTX）的抗癌系统。在将引发基团引入到多糖主链上之后进行聚合物接枝，而不需要保护羟基和避免使用有毒溶剂。设计基于温度响应的葡聚糖共聚物，以表现出自聚集行为，对MTX的亲和力和高细胞内在化。另外，一些接枝的聚合物结合了甲基丙烯酸2-氨基乙酯，以通过离子相互作用增强MTX在胶束中的封装。基于葡聚糖的胶束具有细胞相容性，并具有合适的大小可以用作药物载体。 MTX的释放取决于pH和温度。聚（甲基丙烯酸2-氨基乙基酯）和PNIPAAm与右旋糖酐骨架的结合使MTX在正常生理温度下完全释放。共聚物胶束被肿瘤细胞（CHO-K1）高度内在化，与游离药物相比，当载有MTX时，其细胞毒性增强。
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