In vitro evaluation of N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan for oral insulin delivery

The present investigation explores an oral insulin delivery system based on the modification of chitosan, N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan (HTCC). Synthesis of HTCC was carried out by coupling glycidyl trimethylammonium chloride (GTAC) to chitosan in aqueous medium. Quaternization was confirmed by TNBS assay, FTIR, NMR, SEM studies and zeta potential analysis. Cytotoxicity studies of the derivative were carried out by mu assay and release profile of insulin from HTCC matrix was monitored under in vitro experimental conditions. Further biological activity and conformational stability of released insulin were confirmed using ELISA and circular dichroism studies. Adhesion studies on mucin and freshly excised rat intestinal sections were carried out to evaluate the mucoadhesive nature of the matrix. Confocal microscopy observations showed that these microparticles were capable of opening tight junctions. By exploiting the mucoadhesive and controlled drug releasing capabilities, HTCC particles seems to be a promising candidate for oral insulin delivery. (C) 2010 Elsevier Ltd. All rights reserved.