Fonte Pedro, Araújo Francisca, Reis Salette, Sarmento Bruno
Centro de Investigação em Ciências da Saúde (CICS), Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal.
J Diabetes Sci Technol. 2013 Mar 1;7(2):520-31. doi: 10.1177/193229681300700228.
Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The mainbarriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized.
口服胰岛素可显著改善常规接受皮下注射胰岛素的糖尿病患者的生活质量。事实上，与这种给药途径相比，糖尿病治疗中口服胰岛素具有诸多优势：患者依从性更高、肝脏胰岛素化迅速，且可避免外周高胰岛素血症以及其他不良反应，如可能的低血糖和体重增加。然而，口服胰岛素仍然是一项挑战，因为其口服吸收有限。胰岛素在胃肠道面临的主要障碍是被蛋白水解酶降解以及缺乏穿过肠上皮的转运。已经提出了几种口服胰岛素的策略，但在临床或商业上都没有取得太大成功。将蛋白质封装到纳米颗粒中被认为是一种有前景的口服胰岛素给药替代方法，因为它们有能力促进胰岛素通过细胞旁或跨细胞转运穿过肠黏膜。在这篇综述中，将讨论旨在提高胰岛素口服生物利用度的不同给药系统，特别关注纳米颗粒载体系统，以及制药公司为将首个胰岛素口服给药系统推向市场所做的努力。还将审视给药系统的毒理学和安全性数据、口服胰岛素给药的临床价值和进展以及该研究领域的未来前景。
