Site-specific adaptive nanovesicles for oral insulin delivery

Oral delivery of insulin holds great promise for improving patient compliance. However, the harsh gastrointestinal environment, the low permeability of the intestinal epithelium, and hepatic clearance of foreign particles remain key challenges in this area. Here, we report the site-specific adaptive milk-derived nanovesicles (MiNVs) capable of overcoming intestinal and hepatic barriers for oral insulin delivery. These MiNVs could bind natural IgG on their surface, enabling FcRn-mediated transcytosis by evading the lysosomal degradation pathway. Upon reaching the liver, MiNVs responded to the elevated levels of biothiols in the hepatic microenvironment, triggering site-specific insulin release. In type 1 diabetic rats, the oral bioavailability reached 20.4%, which is about 20-fold higher than that of free insulin. Notably, MiNVs showed effective glycemic control over long-term treatment in type 1 diabetic rat and minipig models. By integrating transepithelial transport and liver-specific responsiveness, the site-specific adaptability of MiNVs supports their promise in oral insulin administration.

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Publication Details

Journal
Science Advances
Published
2025-09-24
DOI
https://doi.org/10.1126/sciadv.ady6386
Citations
7
Primary Topic
RNA Interference and Gene Delivery
Type
article
Field-Weighted Citation Impact
5.64
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article

Site-specific adaptive nanovesicles for oral insulin delivery

Yaru Jia, Jiuheng Shen, Bozhang Xia, Xing‐Jie Liang et al.
7 citations
Science Advances
RNA Interference and Gene Delivery
5.64
article

Site-specific adaptive nanovesicles for oral insulin delivery

Yaru Jia, Jiuheng Shen, Bozhang Xia, Xing‐Jie Liang, W. Sun, Fengfei Xu, Wenlin An, Yubo Fan, Massimo Bottini, Yichen Wan, Yuxuan Zhang, Gang Zhang, Yali Zhang, Jinjin Wang, Jinqiang Wang, Jie Zhong, Zhongbo Hu, Junge Chen, Shaobo Shan, Zhaoqing Zhou
article en
7 citations

Abstract

Oral delivery of insulin holds great promise for improving patient compliance. However, the harsh gastrointestinal environment, the low permeability of the intestinal epithelium, and hepatic clearance of foreign particles remain key challenges in this area. Here, we report the site-specific adaptive milk-derived nanovesicles (MiNVs) capable of overcoming intestinal and hepatic barriers for oral insulin delivery. These MiNVs could bind natural IgG on their surface, enabling FcRn-mediated transcytosis by evading the lysosomal degradation pathway. Upon reaching the liver, MiNVs responded to the elevated levels of biothiols in the hepatic microenvironment, triggering site-specific insulin release. In type 1 diabetic rats, the oral bioavailability reached 20.4%, which is about 20-fold higher than that of free insulin. Notably, MiNVs showed effective glycemic control over long-term treatment in type 1 diabetic rat and minipig models. By integrating transepithelial transport and liver-specific responsiveness, the site-specific adaptability of MiNVs supports their promise in oral insulin administration.

Science AdvancesVol. 11(39)
University of Rome Tor Vergata (IT), Beijing Tian Tan Hospital (CN), National Vaccine and Serum Institute (CN), China National Biotechnology (China) (CN), National Center for Nanoscience and Technology (CN), University of Chinese Academy of Sciences (CN), Zhejiang University (CN), Beihang University (CN)
Openalex Percentile: Top 4%
RNA Interference and Gene Delivery
5.64
DOIOpen Access PDFOpenAlex
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