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

Treating inflammatory bowel disease (IBD) remains a challenge, with many therapies limited by systemic side effects. One promising alternative is to use small extracellular vesicles (EVs)—natural, nanoscale carriers derived from bovine milk that might deliver drugs directly to inflamed gut tissue via the “leaky gut” effect.

This study evaluated the stability and therapeutic potential of these milk-derived EVs in conditions mimicking the human gastrointestinal (GI) tract. While basic characterisation showed no major changes in particle size or charge across different pH levels, more detailed analysis using a membrane-sensitive dye revealed significant lipid bilayer disruption in acidic and enzyme-rich environments. To assess drug behaviour, two small molecules were encapsulated: acridine orange (lipophilic) and riboflavin (hydrophilic). Under GI conditions, acridine orange leaked from the EVs, whereas riboflavin remained protected suggesting these carriers may be more suitable for hydrophilic compounds. However, when tested in a colitis mouse model, unloaded EVs showed no therapeutic effect, regardless of whether they were delivered orally or rectally. These findings highlight the need to look beyond physical characterisation alone and suggest that small milk EVs have limited potential for drug delivery via the GI route in their native form.

Read the full study here.