Nasal absorption and local tissue reaction of insulin nanocomplexes of trimethyl chitosan derivatives in rats

Abstract

The objective of this work was to explore the potential and safety of trimethyl chitosan (TMC) and PEGylated TMC for improved absorption of insulin after nasal administration. The nasal absorption of insulin nanocomplexes of TMC or PEGylated TMC was evaluated in anaesthetized rats. Concomitantly, the histopathological effects of these nanocomplexes on rat nasal mucosa were studied using a perfusion fixation technique. All insulin nanocomplexes containing TMC or PEGylated TMC showed a 34-47% reduction in the blood glucose concentration, when the insulin absorption through the rat nasal mucosa was measured indirectly. In addition, the relative pharmacodynamic bioavailability (F(dyn)) of the formulations was found to be dependent upon the charge ratio of insulin and polymer, regardless of polymer structure. The F(dyn) apparently decreased with increasing charge ratio of insulin : polymer. Although acute alterations in nasal morphology by the formulations were affected by the charge ratio of insulin and polymer, the formulation of insulin/PEGylated TMC nanocomplexes was shown to be less toxic to the nasal epithelial membrane than insulin/TMC nanocomplexes. PEGylated TMC nanocomplexes were a suitable absorption enhancer for nasal delivery of insulin.