Assessing the permeability of supersaturating drug delivery system of amorphous drug-polyelectrolyte/protein nanoplexes in Caco-2 cell monolayer

Solubility enhancements of amorphous drug-polyelectrolyte and drug-protein nanoparticle complexes (nanoplexes) by virtue of their supersaturation generation were established previously. Their permeability across intestinal membrane, however, had not been assessed. The present work evaluated the membrane permeability of amorphous drug-polyelectrolyte/drug-protein nanoplexes across Caco-2 cell monolayer in comparison to the native drugs. Ciprofloxacin (CIP)-dextran sulfate (DXT) and curcumin (CUR)-bovine serum albumin (BSA) were used as the model drug-polyelectrolyte and drug-protein nanoplexes, respectively. The permeability was evaluated for aqueous suspension and granules of the nanoplex. The results showed the CIP-DXT nanoplex exhibited higher apical-to-basal permeability and lower efflux ratio than native CIP, hence higher net CIP absorption. The effect of CIP concentration on permeability was insignificant indicating passive diffusion. The CUR-BSA nanoplex exhibited higher permeability than native CUR in both apical-to-basal and basal-to-apical directions caused by weakened Caco-2 cells' tight junctions in the presence of nanoplex. Efflux ratios of the CUR-BSA nanoplex and native CUR were nonetheless similar. Aqueous suspension and granules of the nanoplex exhibited similar permeability profiles attributed to granules’ good aqueous reconstitution. Importantly, both nanoplexes exhibited similar cytotoxicity towards Caco-2 cells as the native drugs, rendering nanoplex a promising formulation approach for solubility and permeability enhancements.