多肽口服制剂的研究进展──设计策略与产业化挑战

Advances in Oral Peptide Formulations-Design Strategies and Industrialization Challenges

摘要

多肽类药物因特异性较高、药理活性较强且毒性较低，已成为近年来创新药研发的重要方向。与注射给药相比，口服是慢性病患者更为理想的给药方式，但消化道复杂的递送环境和生理屏障严重限制了多肽类药物的口服吸收。围绕多肽口服制剂的关键递送障碍，系统综述了近年来主要制剂策略的研究进展，涵盖肠溶包衣材料与酶抑制剂、吸收促进剂联用的组合体系，黏膜黏附与黏液穿透递药系统、纳米递药系统及药械组合递药系统等，重点分析各制剂策略设计依据、应用优势及现阶段局限。在此基础上，进一步讨论功能性辅料监管、药械组合的人因工程设计与长期安全性评估、生产成本及患者可及性等临床转化与产业化问题。最后，对口服多肽递药技术可能的发展方向及其规模化应用的可行路径进行了归纳。

Abstract

Peptide drugs, due to their high specificity, strong pharmacological activity and relatively low toxicity, have become an important direction in the research and development of innovative drugs in recent years. Compared to injections, oral administration is a more ideal way for patients with chronic diseases; however, the complex delivery environment and multiple physiological barriers in the gastrointestinal tract strictly limit the absorption of oral peptides. Focusing on the key delivery barriers of oral peptide formulations, this review summarizes recent advances in oral peptide formulations, including combination products containing enteric-coating materials, enzyme inhibitors and permeation enhancers, mucoadhesive and mucus-penetrating delivery systems, nanodrug delivery systems, and drug-device combination delivery systems, highlighting their design principles, advantages, and current limitations. On this basis, it further discusses major challenges in clinical translation and industrialization, including supervision of functional excipients, human-factor engineering design and long-term safety assessment of drug-device combinations, manufacturing cost, and patient accessibility, and finally outlines the potential directions for future development and feasible routes toward scalable applications of oral peptide delivery technologies.

关键词

多肽类药物 / 口服给药 / 递药系统 / 产业化

Key words

peptide drug / oral administration / drug delivery system / industrialization

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基金资助

国家自然科学基金区域创新发展联合基金资助项目(U22A20356)