CHITOSAN CAPSULES FOR COLON-SPECIFIC DRUG-DELIVERY - IMPROVEMENT OF INSULIN ABSORPTION FROM THE RAT COLON

The objective of this study was to estimate colon-specific insulin del ivery with chitosan capsules. In vitro drug release experiments from c hitosan capsules containing 5(6)-carboxyfluorescein (CF) were carried out by the Japan Pharmacopoeia (J. P.) rotating basket method with som e slight modifications. The intestinal absorption of insulin was evalu ated by measuring the plasma insulin levels and its hypoglycemic effec ts after oral administration of the chitosan capsules containing insul in and additives. Little release of CF from the capsules was observed in liquid 1, an artificial gastric juice (pH 1), or in liquid 2, an ar tificial intestinal juice (pH 7). However, the release of CF was marke dly increased in the presence of rat cecal contents. A marked absorpti on of insulin and a corresponding decrease in plasma glucose levels wa s observed following the oral administration of these capsules that co ntain 20 IU of insulin and sodium glycocholate (PA% = 3.49%), as compa red with the capsules containing only lactose or only 20 IU of insulin (PA% = 1.62%). The hypoglycemic effect started from 8 h after the adm inistration of chitosan capsules when the capsules entered the colon, as evaluated by the transit time experiments with chitosan capsules. T hese findings suggest that chitosan capsules may be useful carriers fo r the colon-specific delivery of peptides including insulin.