Effect of cationized gelatins on the paracellular transport of drugs through caco-2 cell monolayers

Cationized gelatins, candidate absorption enhancers, were prepared by addition of ethylenediamine or spermine to gelatin and the effects of the resulting ethylenediaminated gelatin (EG) and sperminated gelatin (SG) on the paracellular transport of 5(6)-carboxyfluorescein (CF), FITC-dextran-4 (FD4), and insulin through caco-2 cell monolayers were examined. The Renkin function was used for characterization of the paracellular pathway and changes in the pore radius (R) and pore occupancy/length ratio (ε/L) calculated from the apparent permeability coefficients (Papp) of CF and FD4 are discussed. Ethylenediaminetetraacetic acid (EDTA) increased the R of the caco-2 cell monolayer and the Papp of all compounds examined was markedly increased by the addition of EDTA. On the other hand, EG and SG did not increase R and their enhancing effects were not as strong as those of EDTA. The increase in ε/L could be the enhancing mechanism for the cationized gelatins. The number of pathways for water-soluble drugs, such as CF and FD4, in the caco-2 monolayers could be increased by the addition of the cationized gelatins. The ratios of the permeability coefficients of insulin (observed/calculated based on the Renkin function) suggest that insulin undergoes enzymatic degradation during transport which is not inhibited by enhancers. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association