MUCOADHESIVE POLYMERS IN PERORAL PEPTIDE DRUG-DELIVERY .1. INFLUENCE OF MUCOADHESIVE EXCIPIENTS ON THE PROTEOLYTIC ACTIVITY OF INTESTINAL ENZYMES

In the present study the potency of mucoadhesive excipients to inhibit intestinal proteases has been evaluated. Among the different mucoadhe sive polymers investigated, uniquely the poly(acrylates) polycarbophil and carbomer 934P were able to inhibit the activities of trypsin, alp ha-chymotrypsin, carboxypeptidase A and cytosolic leucine aminopeptida se. However, they failed to inhibit microsomal leucine aminopeptidase and pyroglutamyl aminopeptidase. Carbomer was found to be more efficie nt to reduce proteolytic activity than polycarbophil. The pronounced b inding properties of polycarbophil and carbomer for bivalent cations s uch as zinc and calcium was demonstrated to be a major reason for the observed inhibitory effect. These polymers were able to deprive Ca2+ a nd Zn2+, respectively, from the enzyme structures, thereby inactivatin g their activities. Carboxypeptidase A and alpha-chymotrypsin activiti es were observed to be reversible upon addition of Zn2+ and Ca2+ ions, respectively. It is concluded that poly(acrylates) may be promising e xcipients to protect peptide drugs from intestinal degradation. In com bination with their low toxicity risk they are expected to be suitable excipients for improved peroral delivery of peptide drugs.