Effects of a sperminated gelatin on the nasal absorption of insulin.
The effects of a sperminated gelatin (SG), which was prepared as a candidate absorption enhancer by the addition of spermine to gelatin, on the nasal absorption of insulin, were examined in rats. The AUC of immuno-reactive insulin levels in the plasma after nasal administration of insulin were increased 5.3-fold by addition of 0.2% SG, and the plasma glucose levels fell in a manner dependent on the insulin levels. In Calu-3 cell monolayer permeation experiments, SG showed significant enhancing effects on 5(6)-carboxyfluorescein (CF), FITC-dextran (MW 4400, FD4) and insulin. Evaluation of the tight junctions in the Calu-3 cell monolayers based on the Renkin molecular sieving function suggests that the pore occupancy/length ratio of the permeation pathways for water-soluble molecules in the tight junctions increases, while the equivalent cylindrical pore radius is not changed by SG treatment. SG may transform the true tight junctions, which act as a barrier for water-soluble molecules, into pathways for CF and FD4 to increase their number. SG is a good candidate for a safe absorption enhancer to produce a slight modification of the permeability of the paracellular pathway of mucosal membranes, while retaining the sieving property of the epithelial membranes.
Seki
Toshinobu
T
Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan. toseki@hokuyakudai.ac.jp
Kanbayashi
Hiroshi
H
Chono
Sumio
S
Tabata
Yasuhiko
Y
Morimoto
Kazuhiro
K
D000042:Absorption; D000818:Animals; D019540:Area Under Curve; D005452:Fluoresceins / Q000493:pharmacokinetics; D005780:Gelatin; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000008:administration & dosage*
D005452:Fluoresceins; D007328:Insulin; D013096:Spermine; C024098:6-carboxyfluorescein; D005780:Gelatin