Development and characterization of chitosan succinate microspheres for the improved oral bioavailability of insulin

The present study describes the fabrication of insulin loaded chitosan succinate microspheres to improve the efficacy of orally administered insulin. Chitosan succinate polymer was synthesized and its microspheres were prepared by emulsion phase separation technique. The microspheres were characterized by FT-IR spectroscopy, scanning electron microscopy, particle size, X-ray diffraction, and swelling index. Insulin was loaded into the microspheres by passive absorption technique. The ability of microspheres to protect insulin from gastric enzymatic degradation was investigated. Stability of insulin in the microspheres was determined by gel electrophoresis and circular dichroism (CD). In vitro release studies were performed under simulated gastric and intestinal pH conditions (pH 2.0 and pH 7.4). The pharmacokinetic parameters were monitored after oral administration of insulin loaded chitosan succinate microspheres, chitosan succinate–insulin solution, as well as after subcutaneous injection of insulin to diabetic rats. The degree of succinate substitution in the synthesized polymer was 16%. The prepared microspheres were spherical with an average diameter of 49 ± 2 µm. The insulin-loading capacity was 62%. Chitosan succinate microspheres were found to protect the degradation of insulin from gastric enzymes. The encapsulated insulin was quickly released in simulated intestinal fluid (SIF, pH 7.4), whereas a small fraction of insulin was released in simulated gastric fluid (pH 2.0). The relative pharmacological efficacy for chitosan succinate microspheres (16 ± 4%) was almost fourfold higher than the efficacy of the chitosan succinate–insulin solution administration (4 ± 1.5%). The results suggest that chitosan succinate microspheres could be used as a potential carrier for oral insulin delivery. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3010–3023, 2007