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

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 (R_t) using a group of drug compounds. Results. HT29-18-C₁ develop R_t 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 R_t of ≈300 Ω·cm² and require Ca²⁺-chelation to generate R_t 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 R_t developed from 100–300 Ω·cm² indicating they permeate via the paracellular route. In contrast, ondansetron showed no difference in permeability with changing R_t consistent with transcellular permeation. Permeability profiles across low R_t 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 R_t 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.