多肽类胰高血糖素样肽-1受体激动剂口服递送新技术的研究进展

Progress of Research on New Oral Delivery Technologies for Peptide Glucagon-Like Peptide-1 Receptor Agonists

摘要

口服多肽类胰高血糖素样肽-1 受体激动剂（glucagon-like peptide-1 receptor agonist，GLP-1RA）在糖尿病治疗领域展现出重要临床价值，具有规避低血糖发生风险、提高患者用药依从性、适于长期用药等优势，是当前口服多肽领域的研究热点。然而，胃肠道生理屏障的存在及适宜递送载体的缺乏，严重阻碍了多肽类 GLP-1RA 口服制剂的研发进程。近年来，随着纳米医学等交叉学科的发展，针对多肽类 GLP-1RA 的口服递送策略取得显著进展。综述系统梳理多肽类 GLP-1RA 的研究现状，重点探讨基于多肽类 GLP-1RA 的新型口服递送技术，分析其临床转化过程中的难点，旨在为后续相关研究提供方向性参考。

Abstract

Oral administration of peptide glucagon-like peptide-1 receptor agonists (GLP-1RAs) has demonstrated significant clinical value in diabetes treatment, with such distinct advantages as reduced risk of hypoglycemia, improved patient adherence, and suitability for chronic administration, and has become a research focus in the field of oral peptides. However, the presence of gastrointestinal physiological barriers and the lack of appropriate delivery carriers have significantly hindered the development of oral formulations for peptide GLP-1RAs. In recent years, with the development of interdisciplinary fields such as nanomedicine, remarkable progress has been made in the development of oral delivery strategies for peptide GLP-1RAs. This review systematically summarizes the research status of peptide GLP-1RAs, focuses on the novel oral delivery technologies based on peptide GLP-1RAs, and analyzes the difficulties in their clinical translation, aiming to provide some directional reference for subsequent research.

关键词

胰高血糖素样肽-1 受体激动剂 / 口服递送 / 生物利用度 / 胃肠道屏障

Key words

glucagon-like peptide-1 receptor agonist / oral delivery / bioavailability / gastrointestinal barrier

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基金资助

国家自然科学基金项目(82372113)

国家自然科学基金项目(82373815)

国家高层次青年人才计划资助项目()

江苏省杰出青年基金资助项目(BK20240096)

浙江省自然科学基金联合基金(LKLY25H180014)

临港实验室资助项目(LGL-2614-09)

中央高校基本科研业务费专项资金资助项目(2632025PY02)