Affiliation:
1. School of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin University Tianjin 300350 P. R. China
2. School of Biology and Biological Engineering South China University of Technology Guangzhou 510006 P. R. China
3. Department of Biomedical Engineering The State University of New York at Buffalo Buffalo NY 14260 USA
Abstract
AbstractThe use of orally‐administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal‐IL10‐EVs (C/A) that protects interleukin 10 (IL‐10) from degradation in the stomach and enables targeted delivery of IL‐10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL‐10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL‐10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal‐IL10‐EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal‐IL10‐EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal‐IL10‐EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal‐IL10‐EVs (C/A) features biocompatibility, pH‐responsive drug release, and macrophage‐targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
4 articles.
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