{"title":"通过调节上皮紧密连接增强细胞旁通透性","authors":"Peter D Ward , Tim K Tippin , Dhiren R Thakker","doi":"10.1016/S1461-5347(00)00302-3","DOIUrl":null,"url":null,"abstract":"<div><p>The intestinal epithelium is a major barrier to the absorption of hydrophilic drugs. The presence of intercellular junctional complexes, particularly the tight junctions (<em>zona occludens</em>), 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.</p></div>","PeriodicalId":80125,"journal":{"name":"Pharmaceutical science & technology today","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1461-5347(00)00302-3","citationCount":"217","resultStr":"{\"title\":\"Enhancing paracellular permeability by modulating epithelial tight junctions\",\"authors\":\"Peter D Ward , Tim K Tippin , Dhiren R Thakker\",\"doi\":\"10.1016/S1461-5347(00)00302-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The intestinal epithelium is a major barrier to the absorption of hydrophilic drugs. The presence of intercellular junctional complexes, particularly the tight junctions (<em>zona occludens</em>), 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.</p></div>\",\"PeriodicalId\":80125,\"journal\":{\"name\":\"Pharmaceutical science & technology today\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2000-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S1461-5347(00)00302-3\",\"citationCount\":\"217\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical science & technology today\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1461534700003023\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical science & technology today","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1461534700003023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.