Ubaidulla Udhumansha, Khar Roop Kishan, Ahmad Fahan Jalees, Sultana Yasmin, Panda Amulya Kumar
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India.
J Pharm Sci. 2007 Nov;96(11):3010-23. doi: 10.1002/jps.20969.
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 microm. 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.
本研究描述了载胰岛素琥珀酸壳聚糖微球的制备，以提高口服胰岛素的疗效。合成了琥珀酸壳聚糖聚合物，并通过乳液相分离技术制备了其微球。通过傅里叶变换红外光谱、扫描电子显微镜、粒径、X射线衍射和溶胀指数对微球进行了表征。采用被动吸附技术将胰岛素载入微球。研究了微球保护胰岛素免受胃酶降解的能力。通过凝胶电泳和圆二色性（CD）测定胰岛素在微球中的稳定性。在模拟胃和肠的pH条件（pH 2.0和pH 7.4）下进行体外释放研究。对糖尿病大鼠口服载胰岛素琥珀酸壳聚糖微球、琥珀酸壳聚糖-胰岛素溶液以及皮下注射胰岛素后，监测其药代动力学参数。合成聚合物中琥珀酸取代度为16%。制备的微球呈球形，平均直径为49±2微米。胰岛素载药量为62%。发现琥珀酸壳聚糖微球可保护胰岛素免受胃酶降解。包封的胰岛素在模拟肠液（SIF，pH 7.4）中快速释放，而在模拟胃液（pH 2.0）中有一小部分胰岛素释放。琥珀酸壳聚糖微球的相对药理疗效（16±4%）几乎是琥珀酸壳聚糖-胰岛素溶液给药疗效（4±1.5%）的四倍。结果表明，琥珀酸壳聚糖微球可作为口服胰岛素递送的潜在载体。
