Advances in oral peptide therapeutics
Advances in oral peptide therapeutics
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DOI：
10.1038/s41573-019-0053-0
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发表时间：
2020-04-01
影响因子：
120.1
通讯作者：
Drucker, Daniel J.
中科院分区：
文献类型：
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作者：
Drucker, Daniel J.
肽类药物的口服给药可能有利于治疗依从性，但它面临着与胃肠道的结构组织和生理功能相关的障碍。本文重点介绍了克服这些障碍的策略，并讨论了已进入临床试验的口服肽的经验，包括最近批准的具有里程碑意义的Semaglutide口服制剂用于治疗2型diabetes.Protein和peptide治疗需要胃肠外给药，这可能会阻碍药物依从性。出于这个原因，已经进行了广泛的努力来开发替代的递送策略，特别是对于用于治疗内分泌紊乱的肽如胰岛素。口服递送是特别期望的，但其面临与胃肠道的结构组织和生理功能相关的实质性障碍。本文重点介绍了旨在克服这些障碍的策略，包括渗透增强剂，肠道酶抑制剂，粘液渗透和细胞渗透肽。然后重点介绍已进入临床试验的口服肽类药物的经验，包括胰岛素、降钙素、甲状旁腺激素和加压素，重点介绍最近导致胰高血糖素样肽1受体激动剂semaglutide口服制剂获得里程碑式批准用于治疗2型糖尿病的进展。
Oral delivery of peptide therapeutics could have benefits for treatment adherence, but it faces barriers related to the structural organization and physiological function of the gastrointestinal tract. This article highlights strategies to overcome these barriers and discusses experience with oral peptides that have reached clinical trials, including the recent landmark approval of an oral formulation of semaglutide for the treatment of type 2 diabetes.Protein and peptide therapeutics require parenteral administration, which can be a deterrent to medication adherence. For this reason, there have been extensive efforts to develop alternative delivery strategies, particularly for peptides such as insulin that are used to treat endocrine disorders. Oral delivery is especially desirable, but it faces substantial barriers related to the structural organization and physiological function of the gastrointestinal tract. This article highlights strategies designed to overcome these barriers, including permeation enhancers, inhibitors of gut enzymes, and mucus-penetrating and cell-penetrating peptides. It then focuses on the experience with oral peptides that have reached clinical trials, including insulin, calcitonin, parathyroid hormone and vasopressin, with an emphasis on the advances that have recently led to the landmark approval of an oral formulation of the glucagon-like peptide 1 receptor agonist semaglutide for the treatment of type 2 diabetes.