Rectal Delivery of Insulin Using a Bioadhesive Hydrogel Preparation Containing Lauric Acid as an Enhancer in Rats

Abstract

The rectal delivery of insulin using a bioadhesive hydrogel preparation containing various absorption enhancers was evaluated in rats. Hydrogels were prepared from acrylic block copolymers of methacrylic acid and methacrylate (Eudispert hv). Sodium salts of various fatty acids were incorporated into the hydrogels as absorption enhancers. Sodium oleic acid and 2,6-di-O-methyl-β-cyclo-dextrin (DM-β-CyD) were used as control enhancers. Rectal administration of 50 units kg−1 insulin-loaded 7% (w/w) Eudispert hydrogels containing 5% (w/w) sodium lauric acid (C12) caused a significant (P < 0.01) decrease in plasma glucose levels compared with gels containing 5% DM-β-CyD or sodium oleic acid (43% vs 26 and 17%, respectively), in normal rats. The optimized gel formulation containing C12 was administered to non-insulin-dependent diabetes mellitus (NIDDM) rats. At a dose of 10 units kg−1 insulin, the decrease in plasma glucose levels was significantly (P < 0.05) greater in NIDDM rats compared with normal rats (35 vs 22%, respectively). Bioavailability was approximately 18% in both NIDDM and normal rats. As an index of local toxicity, the amount of protein released from the rectal membrane after administration of hydrogels was measured in normal rats. The amount of protein released for hydrogels containing C12 was significantly (P < 0.05) lower than that for C12 solution. Eudispert hydrogels containing lauric acid may be useful rectal preparations for the delivery of insulin.