Correlation of solute flux across Caco-2 monolayers and colonic tissue in vitro

Caco-2 cells, a human colonic carcinoma cell line, grown as monolayers, have been used extensively to model intestinal absorption. There is currently, however, little information relating transport properties of Caco-2 cell monolayers to colonic tissue. Therefore, we measured the flux rates of a variety of compounds including peptides and proteins across human adeno carcinoma (Caco-2) monolayers and excised rabbit ascending colon. Permeability values were calculated from flux measurements using HPLC, except for proteins, which were analyzed by ELISA or RIA and compared with published permeability data for a series of small molecules. A best fit analysis (R = 0.968) suggested the permeability value for Caco-2 monolayers to be twice that of rabbit colonic tissue. Molecules restricted to the paracellular pathway appeared to have a slightly greater permeability in rabbit colonic tissue when compared with Caco-2 monolayers, whilst hydrophobic compounds, which presumably had access to the transcellular route of transport, had a higher permeability in Caco-2 monolayers. A limited number of normal human sigmoidal colonic biopsy samples were obtained and tested for comparison. From this limited data set, it appeared that permeabilities for human sigmoid colon and rabbit ascending colon were very similar. In summary, these results support the use of Caco-2 cell monolayers as a predictive tool to assess transport properties of solutes across rabbit, and possibly human, colonic tissue in vitro.