通过调节上皮紧密连接增强细胞旁通透性

Peter D Ward , Tim K Tippin , Dhiren R Thakker
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引用次数: 217

摘要

肠上皮是亲水性药物吸收的主要屏障。细胞间连接复合物的存在,特别是紧密连接(闭塞带),使上皮不受亲水性药物的影响,亲水性药物不能通过细胞膜的脂质双分子层在细胞内扩散。在过去的十年里,在理解紧密连接的结构和细胞调节方面取得了重大进展。本文综述了目前关于紧密连接和细胞旁通透性的生理调节的知识,以及通过调节紧密连接有效、安全地增加细胞旁通透性的药物的合理设计的最新进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhancing paracellular permeability by modulating epithelial tight junctions

The intestinal epithelium is a major barrier to the absorption of hydrophilic drugs. The presence of intercellular junctional complexes, particularly the tight junctions (zona occludens), renders the epithelium impervious to hydrophilic drugs, which cannot diffuse across the cells through the lipid bilayer of the cell membranes. There have been significant advances in understanding the structure and cellular regulation of tight junctions over the past decade. This article reviews current knowledge regarding the physiological regulation of tight junctions and paracellular permeability, and recent progress towards the rational design of agents that can effectively and safely increase paracellular permeability via modulation of tight junctions.

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