PERMEABLE SUPPORT TYPE INFLUENCES THE TRANSPORT OF COMPOUNDS ACROSS CACO-2 CELLS

The influence of aluminium oxide and nitrocellulose inserts on the uptake and transport of taurocholic acid in Caco-2 cells has been determined. Caco-2 cells grown on nitrocellulose inserts displayed a higher rate of taurocholic acid transport than those grown on aluminium oxide inserts; 59.3 +/- 4.1 ng 4 h-1 insert-1 compared to 29.7 +/- 4.1 ng 4 h-1 insert-1 at day 14. In addition, Caco-2 cells grown on aluminium oxide and nitrocellulose inserts were not comparable with respect to adsorption potential, cell morphology, cell numbers and transepithelial electrical resistance. The low adsorption potential of aluminium oxide inserts, particularly for high molecular weight or lipophilic ligands such as propranolol and testosterone, allowed basolateral uptake events to be studied with a precision not possible with nitrocellulose inserts. In addition, the translucent nature of aluminium oxide inserts offered significant advantages over the nitrocellulose insert in terms of visualising the cells by light microscopy. Caco-2 cells grown on either type of insert appear fully differentiated when observed by light and electron microscopy. Occasional dome-like structures were present when Caco-2 monolayers were grown on aluminium oxide but not nitrocellulose inserts. Cell numbers were significantly lower on aluminium oxide inserts than on nitrocellulose inserts. Moreover, Caco-2 cells grown on aluminium oxide inserts displayed a higher transepithelial electrical resistance than those grown on nitrocellulose inserts; 871 +/- 149 compared to 513 +/- 32 at day 14. The reasons for these differences and the respective merits of each type of insert are considered.