MUCOADHESIVE POLYMERS IN PERORAL PEPTIDE DRUG-DELIVERY .5. EFFECT OF POLY(ACRYLATES) ON THE ENZYMATIC DEGRADATION OF PEPTIDE DRUGS BY INTESTINAL BRUSH-BORDER MEMBRANE-VESICLES

The purpose of the study was to evaluate the inhibitory effect of the mucoadhesive poly(acrylates) polycarbophil and carbomer on the activit y of proteolytic enzymes bound to the intestinal brush border. To that end, the degradation of a number of peptide drugs in the presence or absence of the poly(acrylates) was investigated, using rat brush borde r membrane vesicles (BBMV) as the protease preparation. Both carbomer and polycarbophil in concentrations of 0.25 and 0.5% (w/v) reduced rat her weakly the enzymatic degradation of the peptide 9-desglycinamide, 8-arginine vasopressin (DGAVP), and only 0.5% (w/v) carbomer inhibited metkephamid degradation, but not polycarbophil. More pronounced inhib itory effects on DGAVP breakdown were found following a 30 min preincu bation of the BBMV suspension with 0.5% (w/v) carbomer. However, the p oly(acrylic acid) derivatives were unable to inhibit the degradation o f buserelin at all. On the other hand, the polypeptide hormone insulin was remarkably stable in the BBMV preparations. In conclusion, the po ly(acrylic acid) derivatives polycarbophil and carbomer show rather we ak inhibitory effects on enzymes of the intestinal brush border cell m embranes responsible for DGAVP and metkephamid degradation.