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Absorption Enhancement of Intrapulmonary Administered Insulin by Various Absorption Enhancers and Protease Inhibitors in Rats

Abstract— The effects of absorption enhancers and protease inhibitors on the pulmonary absorption of insulin were examined by means of an in‐situ pulmonary absorption experiment. Absorption enhancers used in this study were sodium glycocholate, linoleic acid‐surfactant mixed micelles and N‐lauryl‐β‐d‐maltopyranoside whereas aprotinin, bacitracin and soybean trypsin inhibitor were used as protease inhibitors. The absorption of insulin from the lung was evaluated by its hypoglycaemic effect. In the absence of these additives, a slight hypoglycaemic effect was obtained following intrapulmonary administration of insulin. However, we found significant and continuous hypoglycaemic effects after the insulin administration with these additives. N‐Lauryl‐β‐d‐maltopyranoside and bacitracin appeared to be more effective for enhancing the pulmonary absorption of insulin than the other adjuvants. These findings suggest that the use of these two adjuvants would be a useful approach for improving the pulmonary absorption of insulin.