INTESTINAL MUCOSAL TRANSPORT OF INSULIN

The development of an oral dosage form rendering adequate bioavailability (10-20%) of insulin would simplify the lives of diabetics and make intensive treatment easier. Provided that a dosage form is developed to selectively release insulin, it is still likely that intestinal membrane transport and metabolism would remain as barriers to oral insulin delivery. Since the cellular morphology and the enzymatic make-up of the brush-border region vary along the length of the intestine, everted gut sac experiments were performed using segments of the duodenum, jejunum and ileum of the rat small intestine to determine the site(s) where insulin absorption would be optimal. No evidence of active transport processes for insulin was observed. Experiments with intact gut sacs showed no significant degradation of insulin exposed to either the mucosal or serosal tissues. Whole tissue homogenates, however, quickly produced significant losses of insulin. According to the measured flux of insulin across the intestinal mucosa, the duodenum showed very little or no absorption of insulin, while the jejunum and the ileum absorbed low, but significantly greater, amounts of insulin. Mixed micelle solutions, used as absorption enhancers, significantly increased the amount of insulin transported across the intestinal mucosa. Further optimization of the insulin/mixed micelle solutions will be necessary to provide optimal absorption of intact insulin. © 1990.