胰岛素口服给药的困境与突破

The dilemma and breakthrough of oral administration of insulin

糖尿病以高血糖为特征,源于胰岛素缺乏或抵抗,或两者兼有。胰岛素在糖尿病治疗中占据着不可替代的地位。皮下注射是胰岛素的主要给药途径,但患者依从性差,而且存在诸多不良反应。口服胰岛素更安全、更便捷,始终是人们探寻的"圣杯",但由于胰岛素自身的理化性质与体内的吸收屏障,很难达到理想的生物利用度。故本文综述了阻碍胰岛素口服给药的各种吸收屏障,以及近年来在创新药物制剂和生物材料驱动下,胰岛素口服给药领域开展的各种尝试和取得的研究进展。

Diabetes is characterized by hyperglycemia,resulting from insulin deficiency or resistance,or both.Insulin plays an irreplaceable role in the treatment of diabetes.Subcutaneous injection is the main route of insulin administration,but usually leads to poor compliance and many side effects.Oral insulin is safer and more convenient,which has always been the Holy Grail for people to explore.After oral administration,insulin is absorbed into the hepatic portal vein and transported to the liver,which can activate the normal physiological functions and reduce the risk of hypoglycemia,insulin resistance,and improve patient compliance.However,the gastrointestinal tract has multiple absorption barriers such as chemical barrier,enzyme barrier,and permeation barrier.Due to the physical and chemical properties of insulin,it is difficult to achieve desired oral bioavailability.This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials,including structural modification,enzyme inhibitors,absorption enhancers,various nanoparticles,liposomes,microspheres,and even microorganisms.Some clinical researches on oral insulin are also introduced.