Oral TNF-α siRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease

Authors
Han, GeonheeKim, HyosukJang, HochungKim, Eun SunKim, Sun HwaYang, Yoosoo
Issue Date
2024-04
Publisher
Elsevier
Citation
Bioactive Materials, v.34, pp.138 - 149
Abstract
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.
ISSN
2452-199X
URI
https://pubs.kist.re.kr/handle/201004/148509
DOI
10.1016/j.bioactmat.2023.12.010
Appears in Collections:
KIST Article > 2024
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