Cell cultures as tools in biopharmacy

A survey is given on a few selected cell culture models that are used for t ransport studies. They are characterised for growth, transcellular electric al resistance and cytoarchitecture. The importance of standardisation in vi ew of their use as transport models is documented. Their potential for stud ies on passive permeation and P-glycoprotein-mediated transport is explored and related to published data. Transport studies are presented that were p erformed in a two-chamber set-up, the Costar(R) "vertical diffusion system" . A series of non-homologous compounds showed similar permeability data (P- app) in the different cell cultures. The origin of the cell type had no rem arkable influence on passive transcellular permeation. MDCK cells, an epith elial cell line of canine kidney origin, are perfectly suited to screen for passive permeation. They have low expression of transporter proteins and l ow metabolic activity. In general, they probably represent the best-known e pithelial cell line with respect to genetics as well as lipid and protein c omposition. MDCK cells are easy to handle. Transport experiments can be don e between 7 and 14 days after seeding, when the stationary growth phase is reached. To screen for P-glycoprotein substrates, efflux and uptake studies were performed with mdr1-transfected MDCK cells (MDR1-MDCK) in a one-chamb er system in the presence or absence of verapamil or cyclosporin A as inhib itor. Evidence is presented why the transfected cells, which express large amounts of P-glycoprotein, are not suitable for two-chamber transport studi es. (C) 2000 Elsevier Science B.V. All rights reserved.