title: Enhancement of paracellular transport of heparin disaccharide across Caco-2 cell monolayers.
abstract: The enhancement of paracellular transport of heparin disaccharide using several absorption enhancers across Caco-2 cell monolayers was tested. The cytotoxicity of these enhancers was also examined. The enhancing effects by Quillaja saponin, dipotassium glycyrrhizinate, 18beta-glycyrrhetinic acid, sodium caprate and taurine were determined by changes in transepithelial electrical resistance (TEER) and the amount of heparin disaccharide transported across Caco-2 cell monolayers. Among the absorption enhancers, 18beta-glycyrrhetinic acid and taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity. Our results indicate that these absorption enhancers can widen the tight junction, which is a dominant paracellular absorption route of hydrophilic compounds. It is highly possible that these absorption enhancers can be applied as pharmaceutical excipients to improve the transport of macromolecules and hydrophilic drugs having difficulty in permeability across the intestinal epithelium.
authors.affiliation: Natural Products Research Institute, Seoul National University, Korea.
authors.forename: So Yean
authors.initials: SY
authors.lastname: Cho
authors.forename: Jong Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Changkoo
authors.initials: C
authors.lastname: Shim
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000042:Absorption / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D004187:Disaccharides / Q000378:metabolism*; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000378:metabolism; D005079:Excipients; D006493:Heparin / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D004187:Disaccharides; D005079:Excipients; C464536:heparin disaccharide; D008315:Malondialdehyde; D006493:Heparin; D007770:L-Lactate Dehydrogenase