title: Effect of aminated gelatin on the nasal absorption of insulin in rats.
abstract: 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.
authors.affiliation: Hokkaido College of Pharmacy, Otaru, Hokkaido, Japan. toseki@hokuyakudai.ac.jp
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanbayashi
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Nagao
authors.forename: Sumio
authors.initials: S
authors.lastname: Chono
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
mesh_terms: 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
chemical_list: D007328:Insulin; D005780:Gelatin