Validation of the Caco-2 test for intestinal permeability assessment of drugs: the usefulness of papp, the apparent permeability coefficient

摘要

The bioavailability of orally administered drugs depends to a great extent on their capability of being transported across the intestinal barrier. Caco-2 cells, from a human colon adenocarcinoma [1] achieve a high degree of enterocytic differentiation and can be used as an in vitro model for the investigation of drug transport through the intestinal epithelium.The Caco-2 test is based on a static model using a cell monolayer lying on the filter base of a transwell between the apical and the basolateral compartments, both filled with culture medium. These cells, grown onto collagen-coated polycarbonate membrane (transwell), form a monolayer of polarized epithelial cells, which represent a relevant model for the small intestinal epithelium. The process of differentiation starting at cell confluence leads to the formation of a brush border with well-developed micro- villi, tight apical junctions, and a polarized distribution of membrane components, including enzymes, receptors, transport systems, ion channels and lipid molecules. The achievement of complete cell differentiation can be monitored by physical (Transepithelial Electrical Resistance, TEER) and chemical methods.