ENHANCING EFFECTS OF CYCLODEXTRINS ON NASAL ABSORPTION OF INSULIN IN RATS

Nasal administration of bovine insulin in suspension with chemically modified cyclodextrins led to a significant increase in serum immunoreactive insulin levels along with a marked hypoglycemia in rats. Methylated cyclodextrins were more potent enhancers of insulin absorption than the parent and hydroxypropylated cyclodextrins. Spectroscopic observations indicated that the scope of inclusion complexation of insulin with cyclodextrins was limited and appears to be of minor importance in the nasal absorption enhancement. Cyclodextrins increased the permeability of the nasal mucosa, perhaps through the interaction of cyclodextrins with lipids and/or divalent cations on the membrane surface. In addition, the enzymatic degradation of insulin in rat nasal homogenates was suppressed by cyclodextrins. The combination of increased nasal membrane permeability and reduced proteolysis may explain the enhanced nasal absorption of insulin. The present results suggest that chemically modified cyclodextrins, especially the methylated derivatives, may serve as potent absorption enhancers for the nasal delivery of polypeptides.