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 o f 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 as cending colon. Permeability values were calculated from flux measureme nts using HPLC, except for proteins, which were analyzed by ELISA or R IA and compared with published permeability data for a series of small molecules. A best fit analysis (R = 0.968) suggested the permeability value far 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 w ith Caco-2 monolayers, whilst hydrophobic compounds, which presumably had access to the transcellular route of transport, had a higher perme ability in Caco-2 monolayers. A limited number of normal human sigmoid al colonic biopsy samples were obtained and tested for comparison. Fro m this limited data set, it appeared that permeabilities for human sig moid colon and rabbit ascending colon were very similar In summary, th ese results support the use of Caco-2 cell monolayers as a predictive tool to assess transport properties of solutes across rabbit, and poss ibly human colonic tissue in vitro.