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抗糖尿病肽类药物口服给药的新策略——胰岛素、胰高血糖素样肽-1及其类似物。

Novel strategies in the oral delivery of antidiabetic peptide drugs - Insulin, GLP 1 and its analogs.

作者信息

Ismail Ruba, Csóka Ildikó

机构信息

Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.

Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.

出版信息

Eur J Pharm Biopharm. 2017 Jun;115:257-267. doi: 10.1016/j.ejpb.2017.03.015. Epub 2017 Mar 21.

DOI:10.1016/j.ejpb.2017.03.015
PMID:28336368
Abstract

As diabetes is a complex disorder being a major cause of mortality and morbidity in epidemic rates, continuous research has been done on new drug types and administration routes. Up to now, a large number of therapeutic peptides have been produced to treat diabetes including insulin, glucagon-like peptide-1 (GLP-1) and its analogs. The most common route of administration of these antidiabetic peptides is parenteral. Due to several drawbacks associated with this invasive route, delivery of these antidiabetic peptides by the oral route has been a goal of pharmaceutical technology for many decades. Dosage form development should focus on overcoming the limitations facing oral peptides delivery as degradation by proteolytic enzymes and poor absorption in the gastrointestinal tract (GIT). This review focuses on currently developed strategies to improve oral bioavailability of these peptide based drugs; evaluating their advantages and limitations in addition to discussing future perspectives on oral peptides delivery. Depending on the previous reports and papers, the area of nanocarriers systems including polymeric nanoparticles, solid lipid nanoparticles, liposomes and micelles seem to be the most promising strategy that could be applied for successful oral peptides delivery; but still further potential attempts are required to be able to achieve the FDA approved oral antidiabetic peptide delivery system.

摘要

由于糖尿病是一种复杂的疾病,是导致死亡率和发病率呈流行趋势的主要原因,因此一直在对新型药物类型和给药途径进行持续研究。到目前为止,已经生产出大量治疗糖尿病的治疗性肽,包括胰岛素、胰高血糖素样肽-1(GLP-1)及其类似物。这些抗糖尿病肽最常见的给药途径是肠胃外给药。由于这种侵入性途径存在若干缺点,通过口服途径递送这些抗糖尿病肽几十年来一直是制药技术的目标。剂型开发应专注于克服口服肽递送所面临的限制,如被蛋白水解酶降解以及在胃肠道(GIT)中吸收不良。本综述重点关注目前为提高这些基于肽的药物的口服生物利用度而开发的策略;评估它们的优点和局限性,并讨论口服肽递送的未来前景。根据先前的报告和论文,包括聚合物纳米颗粒、固体脂质纳米颗粒、脂质体和胶束在内的纳米载体系统领域似乎是可用于成功口服肽递送的最有前景的策略;但仍需要进一步的潜在尝试,以便能够实现获得美国食品药品监督管理局(FDA)批准的口服抗糖尿病肽递送系统。

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