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[Development of researches in Caco-2 cell model].

The Caco-2 cell model established as a tool for in vitro investigations of intestinal drug transport processes has been widely used because of its growth characteristics, i.e., it forms polarized monolayers in cultures and differentiates into cells with high homology to human intestinal epithelial absorptive cells. Caco-2 cell cultures have provided a major conceptual advance in our understanding of intestinal drug absorption, biotransformation and bioavailability at the cellular level. Caco-2 cells have received considerable attention from the pharmaceutical industry because they have been widely accepted as a potent in vitro model membrane to screen for potential absorption problems in drug discovery programs. However, the Caco-2 monolayers model is still not perfect. The tightness of the monolayers resembles more colonic than small intestinal tissue, resulting in poor permeabilities for hydrophilic compounds traversing the epithelium via the aqueous paracellular pathway. Caco-2 cells have no mucus layer that is a potential barrier to drug absorption and display low expression of cytochrome P450 which are drug metabolizing enzymes. Further refinements of the Caco-2 cell culture model are needed to better predict human intestinal drug transport. To optimize Caco-2 model, the following technics have been used: modifying the condition of the cell culture, using molecular cloning strategies and inducing the expression of relevant enzymes. They are described in this review.