Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier
Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier
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DOI：
10.1016/j.jconrel.2007.09.001
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发表时间：
2007-12-20
影响因子：
10.8
通讯作者：
Preat, V.
中科院分区：
文献类型：
--
作者：
Mathot, Frederic;Rieux, A. Des;Preat, V.
单甲醚聚乙二醇7（50）-聚（己内酯-三亚甲基碳酸酯）（mnnePEG（750）P（CL-co-TMC））可自发形成胶束，通过被动扩散穿过脂质双层，在大鼠体内的口服生物利用度为40%。本工作的目的是研究载药mmePEG（750）P（CL-co-TMC）胶束穿过肠屏障的转运机制。通过破坏紧密连接和抑制内吞作用研究了放射性标记聚合物穿过Caco-2细胞单层的转运。胶束中的聚合物和药物独立地穿过Caco-2细胞单层，并且不使用细胞旁途径或M细胞。聚合物不影响P-gp泵。这一机制的研究表明，而载药胶束被吸收的液相内吞，聚合物单体被动扩散伴随胶束内吞跨膜。(c)2007 Elsevier B. V.保留所有权利。
Monomethylether poly(ethyleneglycol)7(50)-Poly(caprolactone-co-trimethylene carbonate) (mnnePEG(750)P(CL-co-TMC) which spontaneously form micelles, can cross lipid bilayers via passive diffusion and demonstrate an oral bioavailability of 40% in rats. The aim of the current work was to study the transport mechanism(s) of drug-loaded mmePEG(750)P(CL-co-TMC) micelles across the intestinal barrier. The transport of radiolabelled polymer across Caco-2 cell monolayer was investigated by disrupting tight junctions and by inhibiting endocytosis. The polymer and drugs loaded in micelles independently crossed Caco-2 cell monolayers and did not use either the paracellular route or M-cells. The polymer did not affect P-gp pumps. This mechanistic study suggests that whereas drug-loaded micelles were absorbed by fluid-phase endocytosis, polymeric unimers diffused passively across the membrane concomitantly with micellar endocytosis. (c) 2007 Elsevier B.V. All rights reserved.