Oral delivery of synthetic eel calcitonin, elcatonin, in rats

Abstract

This study was designed to develop an oral dosage form of elcatonin (EC), a hypocalcemic peptide. The EC absorption was estimated by the reduction in plasma calcium concentrations. When EC was orally coadministered with nitroso-N-acetyl-D,L- penicillamine (SNAP, 4.0 mg) and 0.02% Carbopol solution or with taurocholate (20 mM) and 0.02% Carbopol solution, the lowering effect was increased compared with that after EC alone, but the F values (0.32 and 0.30%) were extremely small. The oral administration of the mucoadhesive emulsion, which was prepared by coating the W/O/W emulsion with 0.1% Carbopol, enhanced the calcium lowering effect, with the F value of 0.43%. The strong mucoadhesion of the mucoadhesive emulsion to the gastrointestinal mucosa was observed. A capsule containing EC (500 μg), taurocholate (6 mg) and lyophilized Carbopol (3.5 mg) administered orally gave a sustained but comparatively small calcium lowering effect. In the in vitro enzymatic hydrolysis experiment, EC was more rapidly hydrolyzed in the intestinal fluid than in the mucosal extract. The combination of 20 mM taurocholate with 0.02% Carbopol showed the greatest inhibitory effect in both fluid and extract. These data indicated that EC was effectively absorbed through the intestinal wall, but the peptide was dominantly degraded by proteolytic enzymes in the GI tract. These results will offer a potential approach to the oral delivery of EC.