Abstract
In vitro models, either cell-based or tissue-based, are widely used to evaluate the intestinal permeability and absorption of drug substances in early development. The use of excised animal tissue and, more recently, human tissue to study the intestinal permeability of potential drug candidates has several advantages compared with other in vitro tools (e.g., Caco-2 cell monolayer). Preservation of the gut architecture and relative maintenance of physiological conditions (e.g., enzymes, transporters, mucus layer) allow evaluation of several absorption mechanisms in the same model, providing a more realistic correlation with in vivo studies. Other advantages are the possibility of studying regional differences in intestinal absorption and the assessment of drug transport pathways combined with drug metabolism. However, viability and integrity of the excised tissue are important issues to consider. The current review initially gives a brief overview of the anatomy and physiology of the intestine and the main processes involved in intestinal absorption. Then, the chapter discusses current tissue-based methodologies used to evaluate intestinal permeability, with special emphasis on procedures employed in preparing and maintaining the tissue before and during the assay, as well as determinant factors for the success of the experience. Tissue-based models are correlated with in vivo models for intestinal permeability studies. Finally, new trends and challenges in permeability studies using intestinal tissue-based models are addressed.
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