Effects of a sperminated gelatin on the nasal absorption of insulin

• Published in: International journal of pharmaceutics Vol. 338; no. 1; pp. 213 - 218
• Main Authors: Seki, Toshinobu, Kanbayashi, Hiroshi, Chono, Sumio, Tabata, Yasuhiko, Morimoto, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29.06.2007; Elsevier
• Subjects: Absorption; Animals; Area Under Curve; Biological and medical sciences; Fluoresceins - pharmacokinetics; Gelatin; General pharmacology; Insulin; Insulin - administration & dosage; Insulin - pharmacokinetics; Male; Medical sciences; Nasal administration; Nasal Mucosa - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Wistar; Renkin function; Spermine; Spermine - administration & dosage; Nasal administration; Spermine; Gelatin; Insulin; Renkin function; Absorption; Pharmaceutical technology; Intranasal administration; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2007.02.004

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.