Effects of interpenetration of thermo-sensitive gels by crosslinking of chitosan on nasal delivery of insulin: In vitro characterization and in vivo study

This investigation examines the in vitro release of insulin in new thermo-response P-CS/GA/Gly gels, in which a chitosan (CS), crosslinked using glutaraldehyde (GA), interpenetrates Poloxamer (P) gels, and glycine (Gly) is further added to inhibit the crosslinking reactions of GA. The delivery of insulin by nasally administering P-CS/GA/Gly gels in diabetic rats was also examined. The release of insulin from P-CS/GA/Gly gels was significantly sustained (P < 0.01) for about six times longer than release from P gels. The mechanisms of the release of insulin from the gels were consistent with a Fickian diffusion model. The nasal administering of insulin using P-CS/GA/Gly gels in diabetic rats is associated with a greatly prolonged hyperglycemic effect and a pharmacological efficiency (involving the maintenance of the lowest possible blood glucose levels (C_min, 55.5 ± 2.8% of original values, n = 6) for 3 h, with a pharmacological efficiency of 18.0 ± 1.8% (n = 6)) that significantly exceeded those achieved using other gels.