Fondazione IRCCS Istituto Neurologico Carlo Besta, IFOM-IEO-Campus, Milan, Italy.
Maturitas. 2012 Sep;73(1):61-7. doi: 10.1016/j.maturitas.2011.12.004. Epub 2011 Dec 29.
Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients. Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route. In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology. Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy. In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are required for prevention of the disease.
如今,糖尿病(尤其是与西方饮食和生活方式密切相关的 2 型糖尿病)已在全球范围内蔓延成为一种流行病。纳米医学旨在为糖尿病患者的诊断、治疗和即时护理管理提供新的工具。已经开发出几种纳米技术方法来改善依赖胰岛素的糖尿病患者的生活质量。它们通过非侵入性血糖测量以及通过鼻内或口服途径主要以保护和靶向制剂的形式递送来改善脆弱蛋白质的胰岛素给药,从而促进血糖管理。在本综述中,讨论了通过聚合物纳米颗粒进行口服或鼻内胰岛素递送,重点是与疾病(糖尿病)或影响胰岛素释放和生物利用度的与年龄相关的代谢变化相关的生理变化。一个关键问题是,针对某些代谢状况(例如,特定的代谢条件),新一代的靶向纳米颗粒药物正在被开发和优化。这些条件可能会随着年龄或疾病的变化而改变。年龄相关因素的影响,例如非常年幼时的不成熟、老年时的代谢和生理变化或不足的动物模型,不仅在纳米医学中,而且在药理学中都还没有得到充分的研究。总的来说,可以注意到,通过除皮下以外的途径给予的胰岛素的生物利用度相对较低(最大 60%)。此外,像 1 型糖尿病中描述的那样改变肠道通透性或 2 型糖尿病中存在的胰岛素抵抗等其他代谢特殊性等因素也会影响新型纳米药物制剂的开发,并可能导致有前途的动物结果无法成功转化为人类治疗。在未来,用于糖尿病的胰岛素纳米颗粒的开发不仅必须考虑到药物的要求,还必须考虑到疾病或年龄引起的代谢变化。此外,还需要新的方法来预防这种疾病。