Effect of aminated gelatin on the nasal absorption of insulin in rats.
Absorption enhancers, which increase the permeability of drugs through epithelial membranes without damaging them, are especially useful for intranasal administration of peptide drugs. In this study, aminated gelatins, candidate enhancers, having different numbers of amino groups were prepared from gelatin (H-gelatin, isoelectric point = 9.0, MW 100 kDa) and a partial gelatin hydrolysate (L-gelatin, isoelectric point = 8.0, MW 5 kDa), and the enhancing effects on the nasal absorption of insulin, used as a model peptide drug, and 5(6)-carboxyfluorescein (CF), a paracellular marker, were examined in rats. The enhancing effect on insulin and CF depends on the MW and number of amino groups. A high correlation between the enhancing effects on insulin and CF was observed and this suggests that an increase in the paracellular permeability is the mechanism governing the nasal absorption-enhancement of aminated gelatins, at least as far as insulin and CF are concerned. The enhancing mechanism might be shared with other cationic polymers having absorption-enhancing effects.
Seki
Toshinobu
T
Hokkaido College of Pharmacy, Otaru, Hokkaido, Japan. toseki@hokuyakudai.ac.jp
Kanbayashi
Hiroshi
H
Nagao
Tomonobu
T
Chono
Sumio
S
Tomita
Mikio
M
Hayashi
Masahiro
M
Tabata
Yasuhiko
Y
Morimoto
Kazuhiro
K
D000281:Administration, Intranasal; D000586:Amination / Q000187:drug effects; D000818:Animals; D005780:Gelatin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005780:Gelatin