Recently, there is increasing interest in the targeting of peptide and protein drugs to the colon because of the low activity of proteolytic enzymes in the colon. Therefore, many dosage forms such as a time controlled-release dosage form and a pH-sensitive coating dosage form were examined for the specific drug delivery to the colon. However, these approaches have recently been shown to lack site specificity, since the variability of pH and small intestinal transit time of these dosage forms were observed. On the other hand, chitosan, which is one of the polysaccharides widely in nature, is known to be specifically degraded by microorganisms distributed in the colon. In this study, therefore, we prepared chitosan capsules containing insulin and examined the effectiveness of these capsules to colon-specific delivery of insulin. The chitosan capsules containing CF or insulin were obtained from Aicello Chemical Co., Ltd. (Toyohashi, Japan). The mean diameter and weight of these capsules were 3.5 × 1.6 mm and 1.2-1.5 mg, respectively. The surface of these capsules was coated with hydroxypropyl methylcellulose phthalate as enteric coating material. The release studies of drug from the chitosan capsules were carried out using Japan Pharmacopoeia(J. P.) rotating basket method. 5(6)-Carboxyfluorescein (CF), which was encapsulated in the chitosan capsules was used as a water soluble model compound. No release of CF from the capsules was observed in liquid 1 as an artificial gastric juice (pH1) and liquid 2 as an artificial intestinal juice (pH7). However, the release of CF was markedly increased in the presence of rat cecal contents. These findings suggested that the chitosan capsules were degraded by the microorganisms in rat cecal contents. The effectiveness of the chitosan capsules to the colon specific delivery of insulin was investigated by an in vivo absorption experiment. A marked decrease in plasma glucose levels was observed following oral administration of these capsules containing 20 IU insulin and Na-glycocholate, as compared with the capsules containing lactose or insulin only. In addition, the chitosan capsules containing insulin and Na-glycocholate were more effective for reducing the plasma glucose levels than the gelatin capsules containing the same components. Thus, this capsule may be a useful carrier for colon-specific delivery of peptides including insulin.
