MUCOADHESIVE POLYMERS IN PERORAL PEPTIDE DRUG-DELIVERY .2. CARBOMER AND POLYCARBOPHIL ARE POTENT INHIBITORS OF THE INTESTINAL PROTEOLYTIC-ENZYME TRYPSIN

Purpose. The evaluation of the inhibitory action of two mucoadhesive p oly(acrylates), polycarbophil and carbomer, registered by the Food and Drug Administration (FDA), on the intestinal proteolytic enzyme tryps in. Methods. The effect of the polymers on trypsin activity by measuri ng the degradation of a trypsin specific substrate. Binding of Ca2+ io ns and proteins (I-125-BSA) to the poly(acrylates). The influence of t he polymers on the secondary trypsin structure by circular dichroism. Results. Trypsin inhibition was found to be time-dependent upon additi on of Ca2+ in the degradation experiment. Only when Ca2+ was added wit hin 10 min after trypsin incubation, recovery of the enzyme could be o bserved. Both polymers showed a strong Ca2+ binding ability. Carbomer, which had a higher inhibitory effect on trypsin activity, also reveal ed a higher Ca2+ binding affinity than polycarbophil. The amount of Ca 2+ depleted out of the trypsin structure and the reduction of enzyme a ctivity were comparable. Immobilization of trypsin by binding to the p olymers could not be observed at pH 6.7. Circular dichroism studies su ggested that, under depletion of Ca2+ from trypsin, the secondary stru cture changed its conformation, followed by an increased autodegradati on of the enzyme. Conclusions, The poly(acrylates) investigated may ha ve potential to protect peptides from tryptic degradation and may be u sed to master the peroral delivery of peptide drugs.