Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats

Abstract

The absorption enhancing effect of α-, β-, and γ-cyclodextrin (CD), dimethyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DMβCD to the insulin solution resulted in a high bioavailability, 108.9 ± 36.4% (mean ± SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% α-CD gave rise to an insulin bioavailability of 27.7 ± 11.5% (mean ± SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the α-CD-containing solution as compared to the DMβCD preparation. The other CDs, HPβCD (5%), β-CD (1.8%), and γ-CD (5%), did not have significant effects on nasal insulin absorption. DMβCD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DMβCD is a potent enhancer of nasal insulin absorption in rats. © 1991, Plenum Publishing Corporation. All rights reserved.