Buffalo Milk-Derived Extracellular Vesicles Loaded in a Hyaluronic Acid Spray: A Novel Nano-Formulation for Skin Barrier Restoration in Psoriasis

Psoriasis is a chronic inflammatory skin disorder characterized by dysregulation of the immune response, particularly involving activation of the IL-23/Th17 signalling pathway, together with increased oxidative stress and impairment of skin barrier function. These pathogenic mechanisms contribute to persistent inflammation, keratinocyte hyperproliferation, and tissue damage, highlighting the need for innovative therapeutic strategies capable of restoring cutaneous homeostasis. In this study, extracellular vesicles derived from buffalo milk (BM-EVs) were investigated as a natural bioactive platform for skin protection and regeneration. BM-EVs were isolated and extensively characterized, revealing physicochemical properties suitable for topical applications. Metabolomic profiling demonstrated that these vesicles carry a diverse cargo enriched in vitamins and antioxidant-related metabolites, suggesting a potential role in modulating oxidative stress and supporting cellular functions involved in skin repair. To enhance topical delivery and improve retention on the skin surface, BM-EVs were incorporated into a spray formulation based on high-molecular-weight hyaluronic acid (HMW-HA). The resulting formulation exhibited rheological characteristics favourable for atomization and uniform distribution, while also benefiting from the well-known moisturizing, protective, and barrier-supporting properties of hyaluronic acid. The biological activity of BM-EVs was evaluated in human fibroblasts under oxidative stress conditions. The vesicles showed excellent biocompatibility and effectively protected cells from oxidative damage by reducing intracellular reactive oxygen species and limiting lipid peroxidation. These findings suggest that BM-EVs can contribute to the maintenance of redox balance and cellular integrity. BM-EV-loaded HMW-HA spray represents a promising, non-invasive nanomedicine approach for supporting skin homeostasis and mitigating oxidative damage and barrier dysfunction associated with psoriasis.