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Small milk-derived EVs: Suitable vehicles for oral drug delivery?

Seegobin, Nidhi; Taub, Marissa; Vignal, Cécile; Waxin, Christophe; Chris, Victoria; Awad, Atheer; Murdan, Sudaxshina; (2025) Small milk-derived EVs: Suitable vehicles for oral drug delivery? European Journal of Pharmaceutics and Biopharmaceutics , 212 , Article 114744. 10.1016/j.ejpb.2025.114744. Green open access

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Abstract

Current treatments for inflammatory bowel disease often fail due to systemic side effects, but bovine milk-derived extracellular vesicles (EVs) show promise for targeted delivery to inflamed gut tissue via the leaky gut effect. This study assessed the stability of EVs as drug carriers in simulated gastrointestinal (GI) fluids and their efficacy in a colitis mouse model. EVs were characterised after incubation in PBS at various pH levels, and their lipid bilayer stability in biorelevant GI fluids was evaluated using the polar probe laurdan. Two small molecules, acridine orange (lipophilic) and riboflavin (hydrophilic), were loaded into EVs to test their release under GI conditions, while unloaded EVs were investigated for therapeutic effect via oral gavage or rectal enema in a colitis mouse model. Although no significant changes in EVs' physical properties were observed at different pH levels, lipid bilayer damage was evident in acidic (p ≤ 0.05) and enzyme-rich environments (p ≤ 0.01). Acridine orange release was significant (p ≤ 0.05), butriboflavin remained encapsulated, and no therapeutic effect was observed with unloaded EVs in vivo. These results suggest that physical characterisation alone does not reflect EV stability, that bovine milk EVs have limited potential for oral drug delivery and are better suited for hydrophilic drugs.

Type: Article
Title: Small milk-derived EVs: Suitable vehicles for oral drug delivery?
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejpb.2025.114744
Publisher version: https://doi.org/10.1016/j.ejpb.2025.114744
Language: English
Additional information: © 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Bovine milk extracellular vesicles, Hydrophilic cargo, Inflammatory Bowel Disease, Lipophilic cargo, Gastro-intestinal tract
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10208549
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