<I>In Vitro</I> Cell Culture Evaluation and <I>In Vivo</I> Efficacy of Amphiphilic Chitosan for Oral Insulin Delivery

Abstract

The overall goal of this paper was to enhance the bioavailability of orally delivered insulin. A mucoadhesive amphiphilic chitosan derivative, lauroyl sulphated chitosan (LSCS) was used as the oral carrier for insulin. Trans epithelial electrical resistance experiment was performed on Caco-2 cell monolayers and observed a reduction of TEER after the incubation with the particles. The insulin transport experiment was done with excised rat intestinal tissue using an Ussing chamber and observed an enhanced transport of insulin due to the effect of LSCS. Following oral administration of FITC-insulin loaded LSCS in SD rats; the qualitative biodistribution of the administered drug was investigated using a fluorescence microscopy. The results showed the time dependent distribution of insulin through gastro intestinal tract (GIT). The efficacy of insulin-loaded LSCS sub micro particles (LSCS-ins) was investigated in diabetic rats by measuring the blood glucose level and found to be an effective reduction of the blood glucose level after oral administration of LSCS-ins. The pharmacological availability was found to be 2.5-fold and had a longer pharmacological activity compared with that of native insulin via oral and subcutaneous (sc) routes. The enhanced oral bioavailability of insulin may be associated with a higher release rate in the intestinal juice, enhanced absorption by improved permeability and increased residence time in the intestinal cavity. Thus, encapsulating insulin in LSCS matrix is a promising carrier for sustained and controlled drug delivery with improved bioavailability of insulin for diabetic patients.