Varshosaz Jaleh, Sadrai Hassan, Heidari Alireza
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Drug Deliv. 2006 Jan-Feb;13(1):31-8. doi: 10.1080/10717540500309040.
Recently nasal delivery of insulin has gained considerable attention. Some limitations of this route include rapid mucociliary clearance of the drug from the site of deposition resulting in short time span available for absorption and low permeability of the nasal membrane for peptides. The objective of the present study was development of a chitosan bioadhesive gel for nasal delivery of insulin. A nasal perfusion test was used to study the toxicity of 4 absorption enhancers: saponin, sodium deoxycholate, ethylendiamine tetra-Acetic Acid (EDTA) and lecithin. The gels contained 4,000 Iu/dl insulin, 2 or 4% of low and medium molecular weight of chitosan, and lecithin or EDTA. Drug release was studied by a membraneless diffusion method and bioadhesion by a modified tensiometry test. The optimized gel was administered nasally in diabetic rats. The serum insulin levels were analyzed by an insulin enzyme immunoassay kit and serum glucose by glucose oxidase method kits. Formulations containing 2% of low molecular weight of chitosan with EDTA had higher release percentage and dissolution efficiency (DE)(2.5%), lower T(50%) (Time required to release 50% of the drug), mean dissolution time, and bioadhesion than gels containing 4% of medium molecular weight of chitosan with lecithin. Insulin was released by a zero-order kinetic from the gels. The gel of 2% medium molecular weight of chitosan with EDTA caused increase in insulin absorption and reduction the glucose level by as much as 46% of the intravenous route. Considering our in vitro and in vivo studies, the proposed gel formulation could be a useful preparation for controlled delivery of insulin through the nasal route.
最近，胰岛素的鼻腔给药方式受到了广泛关注。该给药途径存在一些局限性，包括药物从沉积部位通过黏液纤毛快速清除，导致可供吸收的时间跨度较短，以及鼻黏膜对肽类的低渗透性。本研究的目的是开发一种用于胰岛素鼻腔给药的壳聚糖生物黏附凝胶。采用鼻腔灌注试验研究了4种吸收促进剂（皂苷、脱氧胆酸钠、乙二胺四乙酸（EDTA）和卵磷脂）的毒性。凝胶中含有4000 Iu/dl胰岛素、2%或4%的低分子量和中分子量壳聚糖以及卵磷脂或EDTA。通过无膜扩散法研究药物释放，通过改良的张力测定试验研究生物黏附性。将优化后的凝胶经鼻腔给予糖尿病大鼠。通过胰岛素酶免疫分析试剂盒分析血清胰岛素水平，通过葡萄糖氧化酶法试剂盒分析血清葡萄糖水平。含有2%低分子量壳聚糖与EDTA的制剂比含有4%中分子量壳聚糖与卵磷脂的凝胶具有更高的释放百分比和溶出效率（DE）（2.5%）、更低的T（50%）（释放50%药物所需的时间）、平均溶出时间和生物黏附性。胰岛素从凝胶中以零级动力学方式释放。含有2%中分子量壳聚糖与EDTA的凝胶使胰岛素吸收增加，血糖水平降低，与静脉给药途径相比降低了多达46%。综合我们的体外和体内研究，所提出的凝胶制剂可能是一种通过鼻腔途径控制胰岛素递送的有用制剂。
