Absorption enhancing effect of cyclodextrins on intranasally administered insulin in rats.
The absorption enhancing effect of alpha-, beta-, and gamma-cyclodextrin (CD), dimethyl-beta-cyclodextrin (DM beta CD), and hydroxypropyl-beta-cyclodextrin (HP beta CD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DM beta CD 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% alpha-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 alpha-CD-containing solution as compared to the DM beta CD preparation. The other CDs, HP beta CD (5%), beta-CD (1.8%), and gamma-CD (5%), did not have significant effects on nasal insulin absorption. DM beta CD 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, DM beta CD is a potent enhancer of nasal insulin absorption in rats.
Merkus
F W
FW
Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
Verhoef
J C
JC
Romeijn
S G
SG
Schipper
N G
NG
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D002642:Chick Embryo; D002923:Cilia / Q000187:drug effects; D003505:Cyclodextrins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003505:Cyclodextrins; D007328:Insulin