Assessment of Transport Barriers Using Cell and Tissue Culture Systems

Abstract

The delivery of the next generation of drugs, particularly polar peptides and proteins, will represent a major challenge to the pharmaceutical scientists. To successfully deliver these potential drugs to specific targets, strategies will have to be developed to circumvent epithelial (e.g., intestinal, buccal, nasal, epidermal) and endothelial (e.g., vascular) cells, which represent both physical and metabolic barriers. This presentation will focus on the possible utility of cultured epithelial and endothelial cells to screen the permeability properties of potential drug candidates, to elucidate transcellular transport mechanisms, to evaluate the potential cellular site of metabolism, and to test strategies to prevent metabolism and/or to enhance the permeability properties of drug candidates. Topics to be discussed include: (a) advantages and disadvantages of cell culture systems; (b) factors important in selecting an appropriate cell culture system which will mimic the in vivo biological barrier; (c) characterization and validation of in vitro cell culture model systems; (d) factors important in selecting a porous membrane and a diffusion apparatus for transcellular transport studies; (e) the effect of cell culturing conditions on the transport characteristics of cultured cells; and (f) factors important in interpretation of in vitro cell culture data.