Liu Xuyang, Teng Xinze, Wang Jiahao, Zhang Gaoshuo, Guo Wen, Zhang Wei, Zhao Qinfu, Hu Cheng, Sun Li, Mao Yuling
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Med-X Center for Materials, Sichuan University, Chengdu 610064, People's Republic of China.
J Control Release. 2025 Jun 17;385:113966. doi: 10.1016/j.jconrel.2025.113966.
The mucosa, as the body's largest immune organ, is involved in various diseases such as ulcerative colitis, respiratory conditions, and tumors. Mucosal delivery offers favorable patient compliance, strong localized therapeutic effects, and the ability to treat a broad spectrum of diseases. However, the multilayered barrier structure of mucosal tissues often hinders effective drug delivery. Although current nanotechnologies have demonstrated some success in overcoming mucosal barriers, they still encounter challenges such as immunogenicity, low stability, high production costs, and difficulties in clinical translation. Extracellular vesicles (EVs), natural nanoscale lipid bilayer vesicles found in plants, animals, microorganisms, and body fluids, possess high biocompatibility, low immunogenicity, targeted delivery, and an excellent capacity to cross biological barriers. Exosomes, a subtype of EVs, are emerging as promising bio-nanotherapeutic tools capable of addressing limitations that conventional nanoparticles cannot. Their cargo of nucleic acids and proteins enables both therapeutic and diagnostic functions across various diseases. Exosomes can effectively traverse mucosal barriers-including gastrointestinal, nasal, and ocular mucosa-thereby offering a potential solution to mucosal delivery challenge. Moreover, exosomes derived from mucosal secretions may serve as biomarkers for diagnosing mucosa-associated diseases, providing a non-invasive and easily accessible alternative to blood samples. This review aims to elucidate the therapeutic roles and mechanisms of exosomes from different sources as drug carriers or therapeutic agents in diseases treated via transmucosal delivery. It also summarizes the diagnostic potential of mucosal secretion-associated exosomes. In conclusion, this paper underscores the importance of exosomes in mucosal delivery, discusses their current limitations and future promise, and provides new insights into their clinical applications.
黏膜作为人体最大的免疫器官，参与多种疾病的发生发展，如溃疡性结肠炎、呼吸道疾病和肿瘤等。黏膜给药具有患者顺应性好、局部治疗效果强以及能治疗多种疾病的特点。然而，黏膜组织的多层屏障结构常常阻碍药物的有效递送。尽管目前的纳米技术在克服黏膜屏障方面已取得一些成功，但仍面临免疫原性、稳定性低、生产成本高以及临床转化困难等挑战。细胞外囊泡（EVs）是在植物、动物、微生物和体液中发现的天然纳米级脂质双分子层囊泡，具有高生物相容性、低免疫原性、靶向递送能力以及出色的跨越生物屏障的能力。外泌体作为EVs的一种亚型，正成为有前景的生物纳米治疗工具，能够解决传统纳米颗粒无法解决的局限性。它们携带的核酸和蛋白质赋予了其在多种疾病中的治疗和诊断功能。外泌体能够有效穿越黏膜屏障，包括胃肠道、鼻腔和眼部黏膜，从而为黏膜给药挑战提供了潜在的解决方案。此外，源自黏膜分泌物的外泌体可作为诊断黏膜相关疾病的生物标志物，为血液样本提供了一种非侵入性且易于获取的替代方法。本综述旨在阐明不同来源的外泌体作为药物载体或治疗剂在经黏膜给药治疗疾病中的治疗作用和机制。它还总结了黏膜分泌相关外泌体的诊断潜力。总之，本文强调了外泌体在黏膜给药中的重要性，讨论了它们目前的局限性和未来前景，并为其临床应用提供了新的见解。
