Comparison of HT29-18-C1 and Caco-2 Cell Lines as Models for Studying Intestinal Paracellular Drug Absorption

Publisher Website
Google Scholar
Abstract
Purpose. To compare the permeability characteristics of HT29-18-C1 colonic epithelial cell line with Caco-2, an established model of intestinal drug transport. Methods. Cell lines were grown as epithelial monolayers. Permeability was measured over a range of transepithelial electrical resistance (Rt) using a group of drug compounds. Results. HT29-18-C1 develop Rt slowly when grown in culture, allowing permeability to be measured over a wide range (80–600 Ω·cm2). In contrast, Caco-2 monolayers rapidly develop Rt of ≈300 Ω·cm2 and require Ca2+-chelation to generate Rt equivalent to human intestine (60–120 Ω·cm2). Permeability of atenolol, ranitidine, cimetidine, hydrochlorothiazide and mannitol across HT29-18-C1 decreased 4–5 fold as Rt developed from 100–300 Ω·cm2 indicating they permeate via the paracellular route. In contrast, ondansetron showed no difference in permeability with changing Rt consistent with transcellular permeation. Permeability profiles across low Rt HT29-18C1 and pulse EGTA-treated Caco-2 monolayers were the same for all 5 paracellular drugs suggesting that transient Ca2+ removal does not alter selectivity of the tight junctions. Permeabilities of cimetidine, hydrochlorothiazide and atenolol across 100 Ω·cm2 HT29-18-C1 monolayers reflect more closely those reported for the human ileum in vivo than did mature Caco-2 monolayers. Conclusions. HT29-18-C1 monolayers can be used to study drug permeability at Rt values similar to human intestine without the need for Ca2+ chelation. As such, they offer a useful alternative to Caco-2 for modelling intestinal drug absorption.