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当今聚合技术的发展为合成各种非线形两亲性聚合物提供了手段,对于包载模型药物的杂臂聚合物胶束的摄取和跨膜转运却鲜有报道。本文对两种不同分子量的PEO-(hb-PG)-g-PCL杂臂聚合物胶束的物理性质和Caco-2细胞对其包载的香豆素-6(C6)的摄取量进行了比较,随后选择了PEO113-(hb-PG)15-g-PCL22聚合物胶束来研究PMs-C6在Caco-2单层的摄取和转运。细胞摄取和跨膜转运试验发现,对于Caco-2细胞单层,PMs是很好的摄取和跨膜转运促进剂。对内吞通路的研究发现,PMs-C6的摄取是通过小窝蛋白介导的内吞途径而非网格蛋白介导的内吞途径进行的。本文中制备的PEO-(hb-PG)-g-PCL杂臂聚合物胶束有较小的临界胶束浓度,对Caco-2细胞无显著细胞毒性,以及强大的增加Caco-2细胞单层对疏水性荧光探针C6摄取的作用提示很有潜力用于口服药物递送。
The current development of polymerization technology provides a means for the synthesis of various non-linear amphiphilic polymers. However, few reports have been reported on the uptake and transmembrane transport of the tethered polymeric micelles containing the model drug. In this paper, the physical properties of two different molecular weight PEO- (hb-PG) -g-PCL arm-arm polymeric micelles and the uptake of coumarin-6 (C6) by Caco-2 cells The PEO113- (hb-PG) 15-g-PCL22 polymer micelles were subsequently selected to study the uptake and transport of PMs-C6 in the Caco-2 monolayer. Cell uptake and transmembrane transport assays found that PMs are good uptake and transmembrane transport enhancers for Caco-2 cell monolayers. Studies of the endocytosis pathway found that PMs-C6 uptake was mediated by caveolin-mediated endocytosis rather than clathrin-mediated endocytosis. The prepared micelles of PEO- (hb-PG) -g-PCL had less critical micelle concentration, no significant cytotoxicity on Caco-2 cells, and a strong increase of Caco-2 cell monolayer The effect on hydrophobic fluorescent probe C6 uptake suggests great potential for oral drug delivery.