Bock, U., Haltner, E., U. Schafer, and C-M Lehr. In Vitro Models Based on Human Epithelial Cells and Tissues to Study Drug Absorption and Permeability. ATLA 1999. 27:86.

Combinatorial chemistry and pharmacological high throughput screening, allow the generation of high numbers of potential drug candidates. At the same time, biotechnology is generating an increasing number of peptides, proteins, and gene vectors, which require advanced technologies for the safe and efficient delivery across biological barriers. In our laboratories, we have established and characterized an array of in vitro models representing the biological absorption barriers for the most relevant routes of drug delivery, i.e. the GI tract, the lungs and the skin. As a model for the GI-mucosa, we are using the Caco-2 cell line that is well established in the pharmaceutical sciences and has an excellent in vitro/in vivo correlation. For the respiratory tract, we are using either human alveolar cell lines (for example, A549) or human alveolar epithelial cells in primary culture. Recently, we have succeeded in growing monolayers of human alveolar epithelial cells, displaying type-I cell characteristics and functional tight junctions. To study dermal penetration and permeation, we are using native human skin biopsies, which are either mounted in our specially designed “Saarbrucker skin model” or in Franz diffusion cells. Drug extraction and analysis in tape strips and surface-parallel skin cryosections enables us to identify drug distribution and metabolism in the different skin layers. We have compared both of these ex vivo models with in vivo data from humans to show the suitability of the different models. These in vitro models can be used as a further screening parameter for possible drug candidates, and also to examine the transport mechanism of established drugs.