Effects of superporous hydrogels on paracellular drug permeability and cytotoxicity studies in Caco-2 cell monolayers

The aim of this study was to evaluate the effect of superporous hydrogel (SPH) and SPH composite (SPHC) as permeation enhancers for peptide drug delivery on Caco-2 cell monolayers. Moreover, the cytotoxic effects of these polymers were also studied using trypan blue test, MTT assay and propidium iodide staining. Transepithelial electrical resistance (TEER) studies revealed that both SPH and SPHC polymers were able to decrease TEER values to about 40% of initial values, indicating the ability of these polymers to open tight junctions. Recovery studies of TEER showed that the effects of polymers on Caco-2 cell monolayers were reversible, indicating viability of the cells after incubation with polymers. Both polymers were able to enhance the transport of the hydrophilic marker C-14-mannitol up to 2.7 and 3.8-fold in comparison to the control group. The cumulative transport of fluorescein isothiocyanate labelled dextrans with a molecular weight of 4400 Da (FD4) and 19 600 Da (FD20) was enhanced by SPH and SPHC polymers by opening of tight junctions; however, this enhancement was inversely proportional to the molecular weight of marker compounds. Cytotoxicity studies confirmed that the transport enhancing properties of SPH and SPHC polymers were not caused by damage of the Caco-2 cell monolayers. The cells were able to exclude trypan blue as well as propidium iodide after incubation with SPH and SPHC polymers. MTT assay showed that the number of viable cells was higher than 95% after incubation with SPH and SPHC polymers. This indicates that the mitochondrial metabolic activities of the cells were preserved after application of the polymers. (C) 2002 Elsevier Science B.V. All rights reserved.