Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles.
OBJECTIVE
To investigate whether the widely accepted advantages as sociated with the use of chitosan as a nasal drug delivery system might be further improved by application of chitosan formulated a nanoparticles.


METHODS
Insulin-chitosan nanoparticles were prepared by the ionotropic gelation of chitosan glutamate and tripolyphosphate pentasodium and by simple complexation of insulin and chitosan. The nasal absorption of insulin after administration in chitosan nanoparticle formulations and in chitosan solution and powder formulations wa evaluated in anaesthetised rats and/or in conscious sheep.


RESULTS
Insulin-chitosan nanoparticle formulations produced a pharmacological response in the two animal models, although in both cases the response in terms of lowering the blood glucose levels was less (to 52.9 or 59.7% of basal level in the rat, 72.6% in the sheep than that of the nasal insulin chitosan solution formulation (40.1% in the rat, 53.0% in the sheep). The insulin-chitosan solution formulation was found to be significantly more effective than the complex and nanoparticle formulations. The hypoglycaemic response of the rat to the administration of post-loaded insulin-chitosan nanopar ticles and insulin-loaded chitosan nanoparticles was comparable. As shown in the sheep model, the most effective chitosan formulation for nasal insulin absorption was a chitosan powder delivery system with a bioavailability of 17.0% as compared to 1.3% and 3.6% for the chitosan nanoparticles and chitosan solution formulations, respectively.


CONCLUSIONS
It was shown conclusively that chitosan nanoparticles did not improve the absorption enhancing effect of chitosan in solution or powder form and that chitosan powder was the most effective for mulation for nasal delivery of insulin in the sheep model.
West Pharmaceutical Services, Drug Delivery & Clinical Research Centre Ltd, Albert Einstein Centre, Nottingham, United Kingdom.
A M
AM
Dyer
M
M
Hinchcliffe
P
P
Watts
J
J
Castile
I
I
Jabbal-Gill
R
R
Nankervis
A
A
Smith
L
L
Illum
D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D023421:Models, Animal; D036103:Nanotechnology / Q000379:methods*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep
D007328:Insulin; D019999:Pharmaceutical Solutions; D011208:Powders; D002686:Chitin; D048271:Chitosan