Chitosan as a nasal delivery system: Evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models

The ability of a range of chitosans to act as nasal peptide absorption promoter systems was investigated using the rat nasal absorption model described by Illum et al. (1989). The systemic absorption of insulin was monitored indirectly by measuring arterial blood glucose levels. All five chitosans evaluated produced clinically relevant levels of insulin in the blood. The effect on nasal epithelial membranes of circulating 0.25% w/v chitosan solutions, was investigated using the rat nasal perfusion method. Perfusate samples were assayed for total protein content, the membrane-bound enzyme 5'-nucleotidase (5'ND) and the cytosolic enzyme lactate dehydrogenase (LDH). All the chitosans tested caused minimal membrane and cellular damage when compared to the membrane destruction caused by perfusing a 1% w/v Laureth 9 solution. The time dependent increase in perfusate protein content observed was suggested to be due to the interaction of chitosan with mucin on the membrane surface.