Han, Geonhee Kim, Hyosuk Jang, Hochung Kim, Eun Sun Kim, Sun Hwa Yang, Yoosoo 2024-02-07T05:10:48Z 2024-02-07T05:10:48Z 2024-02-01 2024-04 https://pubs.kist.re.kr/handle/201004/148509 Oral administration facilitates the direct delivery of drugs to lesions within the small intestine and colon, making it an ideal approach for treating patients with inflammatory bowel disease. However, multiple physical barriers impede the delivery of oral RNA drugs through the gastrointestinal tract. Herein, we developed a novel oral siRNA delivery system that protects nucleic acids in extreme environments by employing exosomes derived from milk to encapsulate tumor necrosis factor-alpha (TNF-α) siRNA completely. The remarkable structural stability of milk-derived exosomes (M-Exos), as opposed to those from HEK293T cells, makes them exceptional siRNA carriers. Results demonstrate that milk exosomes loaded with TNF-α siRNA (M-Exo/siR) can effectively inhibit the expression of TNF-α-related inflammatory cytokines. Moreover, given that milk exosomes are composed of unique lipids with high bioavailability, orally administered M-Exo/siR effectively reach colonic tissues, leading to decreased TNF-α expression and successful alleviation of colitis symptoms in a dextran sulfate sodium-induced inflammatory bowel disease murine model. Hence, milk-derived exosomes carrying TNF-α siRNA can be effectively employed to treat inflammatory bowel disease. Indeed, using exosomes naturally derived from milk may shift the current paradigm of oral gene delivery, including siRNA. English Elsevier Oral TNF-α siRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease Article 10.1016/j.bioactmat.2023.12.010 1 Bioactive Materials, v.34, pp.138 - 149 Bioactive Materials 34 138 149 Y scie scopus 001225701500001 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article MEMBRANES CELLS MOLECULAR-DYNAMICS SIMULATIONS TUMOR-NECROSIS-FACTOR Inflammatory bowel disease TNF-alpha Milk-derived exosome Oral gene delivery siRNA