Predictive modeling of insulin release profile from cross-linked chitosan microspheres

Insulin-loaded microspheres composed of chitosan 3% (w/v), and loading 120 IU insulin were produced by emulsion cross-linking method. Cross-linking time was 5 h and glutaraldehyde 3.5% (v/v) was used as cross-linker. Swelling ratio studies were evaluated to predict release of insulin from chitosan microspheres. Bacitracin and sodium taurocholate were incorporated in the formulations as proteolytic enzyme inhibitor and absorption enhancer, respectively. In vitro insulin release studies were performed in phosphate buffer pH 7.4 and also in HCl pH 2 with and without trypsin. Activity of bacitracin was also evaluated. In vitro release showed a controlled profile up to 12 h and the formulation containing 0.15% (w/v) of bacitracin revealed a maximum biological activity of about 49.1 ± 4.1%. Mathematical modeling using Higuchi and Korsmeyer–Peppas suggested a non-Fickian diffusion as the mechanism of insulin release. Insulin-loaded chitosan microspheres for oral delivery showed to be an innovative and reliable delivery system to overcome conventional insulin therapy.

Graphical abstractIn vitro insulin release studies of 120 IU insulin loading cross-linked chitosan microspheres were performed in phosphate buffer pH 7.4 containing trypsin. Activity of bacitracin was also evaluated. In vitro release showed a controlled profile up to 12 h and the formulation containing 0.15% (w/v) of bacitracin revealed a maximum biological activity of about 49.1 ± 4.1%. Mathematical modeling following Higuchi and Korsmeyer–Peppas suggested a non-Fickian diffusion as the mechanism of insulin release.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Insulin release was analyzed by zero order, first order, Higuchi and Korsmeyer–Peppas models. ► Cross-linked chitosan microspheres promoted a slow swelling at pH 2. ► Following Korsmeyer–Peppas model, the diffusional release was reported non-Fickian.