Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats

Abstract

The objective of the present study was to evaluate the effects of formulation parameters on the in vivo pharmacological activity of the chitosan-insulin nanoparticles. Chitosan-insulin nanoparticles were prepared by ionotropic gelation at pH 5.3 and 6.1 and denoted as F5.3np and F6.1np, respectively. F5.3np and F6.1np administered orally at insulin doses of 50 U/kg and/or 100 U/kg were effective at lowering the serum glucose level of streptozotocin-induced diabetic rats. The 100 U/kg-dose F5.3np sustained the serum glucose at pre-diabetic levels for at least 11 h. In comparison, F6.1np had a faster onset of action (2 h versus 10 h) but lower efficiency. The effectiveness of peroral F5.3np and F6.1np in lowering the serum glucose level of streptozotocin-induced diabetic rats was ascribed to the local effect of insulin in intestine. Confocal micrographs showed strong interaction between rat intestinal epithelium and chitosan nanoparticles 3 h post-oral administration. © 2005 Elsevier B.V. All rights reserved.