REQUINTE, Department of Chemical Sciences-Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal.
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal; ICBAS-Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland.
Biotechnol Adv. 2015 Nov 1;33(6 Pt 3):1342-54. doi: 10.1016/j.biotechadv.2015.02.010. Epub 2015 Feb 26.
Diabetes mellitus is a high prevalence and one of the most severe and lethal diseases in the world. Insulin is commonly used to treat diabetes in order to give patients a better life condition. However, due to bioavailability problems, the most common route of insulin administration is the subcutaneous route, which may present patients compliance problems to treatment. The oral administration is thus considered the most convenient alternative to deliver insulin, but it faces important challenges. The low stability of insulin in the gastrointestinal tract and low intestinal permeation, are problems to overcome. Therefore, the encapsulation of insulin into polymer-based nanoparticles is presented as a good strategy to improve insulin oral bioavailability. In the last years, different strategies and polymers have been used to encapsulate insulin and deliver it orally. Polymers with distinct properties from natural or synthetic sources have been used to achieve this aim, and among them may be found chitosan, dextran, alginate, poly(γ-glutamic acid), hyaluronic acid, poly(lactic acid), poly(lactide-co-glycolic acid), polycaprolactone (PCL), acrylic polymers and polyallylamine. Promising studies have been developed and positive results were obtained, but there is not a polymeric-based nanoparticle system to deliver insulin orally available in the market yet. There is also a lack of long term toxicity studies about the safety of the developed carriers. Thus, the aims of this review are first to provide a deep understanding on the oral delivery of insulin and the possible routes for its uptake, and then to overview the evolution of this field in the last years of research of insulin-loaded polymer-based nanoparticles in the academic and industrial fields. Toxicity concerns of the discussed nanocarriers are also addressed.
糖尿病是一种高患病率的疾病，也是世界上最严重和致命的疾病之一。胰岛素通常用于治疗糖尿病，以改善患者的生活条件。然而，由于生物利用度问题，胰岛素最常见的给药途径是皮下途径，这可能会导致患者对治疗的依从性问题。因此，口服给药被认为是输送胰岛素的最方便的替代方法，但它面临着重要的挑战。胰岛素在胃肠道中的稳定性低和低肠渗透是需要克服的问题。因此，将胰岛素包封在基于聚合物的纳米粒子中被认为是提高胰岛素口服生物利用度的一种很好的策略。在过去的几年中，已经使用了不同的策略和聚合物来包封胰岛素并进行口服给药。已经使用了具有天然或合成来源的不同特性的聚合物来实现这一目标，其中可能包括壳聚糖、葡聚糖、海藻酸盐、聚（γ-谷氨酸）、透明质酸、聚乳酸、聚（乳酸-共-乙醇酸）、聚己内酯（PCL）、丙烯酸聚合物和聚烯丙胺。已经开发了有前途的研究并取得了积极的结果，但目前市场上还没有用于口服递送胰岛素的基于聚合物的纳米粒子系统。关于所开发载体的安全性的长期毒性研究也缺乏。因此，本综述的目的首先是深入了解胰岛素的口服递送及其可能的吸收途径，然后概述近年来在学术和工业领域研究载有胰岛素的基于聚合物的纳米粒子方面的这一领域的进展。还讨论了所讨论的纳米载体的毒性问题。
