Development a multicellular model to investigate the intestinal-vascular transport barrier of drug

Abstract

Multicellular transport models for drug have received more attention and research due to a closer physiological structure. A Caco-2/EA.hy926 cell co-culture model was constructed to simulate intestinal-vascular barrier. The morphology of microvilli-like and desmosomes structure indicated the tight connection of Caco-2 cells. The apparent permeability coefficient value of phenol red (≤1 × 10−6 cm/s), trans-epithellal electric resistance value (≥300 Ω cm2) and the alkaline phosphatase activity ratio of AP to BL side presented a confluent and integral cell monolayer with well-established differentiation. The microscopic images and vascular endothelial cadherin expression demonstrated the adhesion junction between EA.hy926 cells. The constructed multicellular model differentiated drug transport behavior. The transport potential of EA.hy926 and Caco-2 cells was similar for daidzein and different for daidzin. Combined with multiple evaluation indexes, it could track the multicellular transport process of nanoparticles. The new multicellular model exhibited more in vivo-like characteristics and architecture from intestine to blood, and a potential improvement of in vitro absorption and transport models for drug.