Enhancement of paracellular transport of heparin disaccharide across Caco-2 cell monolayers.
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.
Cho
So Yean
SY
Natural Products Research Institute, Seoul National University, Korea.
Kim
Jong Sik
JS
Li
Hong
H
Shim
Changkoo
C
Linhardt
Robert J
RJ
Kim
Yeong Shik
YS
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
D004187:Disaccharides; D005079:Excipients; C464536:heparin disaccharide; D008315:Malondialdehyde; D006493:Heparin; D007770:L-Lactate Dehydrogenase