Oral administration properties and physiological functions evaluation of extracellular vesicles derived from colostrum and mature milk

Milk extracellular vesicles (mEVs) derived from colostrum (C-mEVs) and mature milk (M-mEVs) have been proposed as oral drug delivery platforms and potential nanomedicines. However, their differences in oral administration properties and physiological functions have not yet been documented. Here, we comprehensively evaluated the biological properties and physiological functions of C-mEVs and M-mEVs, emphasizing their storage stability, gastrointestinal tolerability, and functional differences revealed through small RNA sequencing. Our findings showed that both C-mEVs and M-mEVs exhibit excellent stability at 4 and –80 ℃ over 1 month. Furthermore, C-mEVs, characterized by their smaller size, demonstrated greater tolerance to harsh digestive environments compared to M-mEVs. For physiological functions, both C-mEVs and M-mEVs suppressed inflammation, protected epithelial barrier integrity, and mitigated oxidative stress damage. Notably, M-mEVs displayed enhanced anti-inflammatory and antioxidative effects. Taken together, M-mEVs hold potential as nanotherapeutic agents for immunoinflammatory diseases, while C-mEVs may serve as a promising oral drug delivery platform.