Hang Ning,1,* Xinyu Huang,1,* Na Deng,2 Xiaoyuan Lin,1 Ling Zheng,2 Ying Zhu,1 Yin Xu1 

1The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yin Xu, The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China, Tel +86-13787262655, Email 311118@hnucm.edu.cn

Abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease, the incidence of which continues to rise globally, and existing therapeutic options are limited by low drug bioavailability and systemic side effects. In this study, we systematically investigated the challenges of the special gastrointestinal environment of UC patients for oral drug delivery, such as extreme pH, degradation by digestive enzymes, metabolism of intestinal flora and obstruction of the intestinal mucosal barrier, and summarized the potential of plant-derived Exosome-like Nanovesicles (PELNs) as a novel delivery system. PELNs are produced by plant cells and mainly consist of proteins, RNA, lipids and plant active molecules. Animal and cell experiments have shown that they can treat UC through the regulation of the intestinal bacterial flora, the inhibition of inflammatory pathways, and the promotion of mucosal repair, etc. On the other hand, their small particle size (30– 500 nm), negative charge and lipid bilayer structure enable them to penetrate the intestinal mucus layer, tolerate extreme pH and enzymatic degradation, and adhere to intestinal epithelial cells through electrostatic interactions, thus possessing advantages such as low immunogenicity, high stability and natural targeting. Furthermore, the engineering modification of PELNs can significantly enhance targeting and therapeutic efficacy, such as surface modification or drug loading. Future research should focus on the systematic characterization, safety validation, large-scale production and multimodal combination therapy of PELNs in order to promote their clinical translation, which not only provides an efficient delivery platform for the treatment of UC, but also opens up a new pathway for the development of natural medicines.

Keywords: ulcerative colitis, exosome-like nanovesicles, natural products, oral drug delivery, research progress