CICS, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal.
Expert Opin Drug Deliv. 2012 Dec;9(12):1539-58. doi: 10.1517/17425247.2012.737779. Epub 2012 Oct 25.
Insulin has usually been administered subcutaneously in the treatment of diabetes mellitus. Alternative delivery routes of insulin are expected to overcome some limitations, mainly concerned with the possibility of hypoglycemia episodes, weight gain and inadequate post-meal glucose control, in order to lead a better patient compliance.
This review article covers all the most relevant non-invasive insulin delivery methods under development, respective technology and clinical data available according to their status of development. Special focus is given to the systems with late clinical trial evidences, their achievements and pitfalls. Pulmonary and oral appear to be the most advantageous routes, with regard to the long list of potentially marketed products.
Alternative insulin delivery to the subcutaneous administration is more and more close to the success, being fundamental that any optimized technology could overcome the overall low mucosal bioavailability of insulin, mostly due to its early degradation before absorption, inactivation and digestion by proteolytic enzymes and poor permeability across mucosal epithelium because of its high molecular weight and lack of lipophilicity.
胰岛素通常用于治疗糖尿病患者的皮下注射。替代胰岛素的给药途径有望克服一些限制,主要涉及低血糖发作、体重增加和餐后血糖控制不足的可能性,以提高患者的依从性。
本文综述了所有正在开发的最相关的非侵入性胰岛素传递方法,根据其发展阶段,介绍了各自的技术和临床数据。特别关注具有后期临床试验证据的系统,以及它们的成就和缺陷。就潜在上市产品的数量而言,肺部和口服途径似乎是最有利的途径。
替代胰岛素的皮下注射给药方式越来越接近成功,任何优化的技术都必须克服胰岛素整体黏膜生物利用度低的问题,主要是因为其在吸收、失活和消化之前被蛋白酶过早降解,以及由于其分子量高和缺乏亲脂性,穿过黏膜上皮的渗透性差。