Liposomal fusion of plant-based extracellular vesicles to enhance skin anti-inflammation

This study reports a hybrid extracellular vesicle (EV)/liposome system developed through vesicular membrane fusion between anti-inflammatory Hydrangea macrophylla leaf EVs (HML-EVs) and terpinen-4-ol/azelamide monoethanolamine-loaded liposomes. Successful liposomal fusion between HML-EVs and terpinen-4-ol/azelamide monoethanolamine-loaded-liposome membranes, confirmed using the two-color fluorescence resonance energy transfer mechanism, enabled the scaled production of a stable hybrid HML-EV/liposome dispersion at a length scale of 100–200 nm. We show that the hybrid EV/liposome significantly inhibits apoptosis by nitric oxide and tumor necrosis factor-α production. Furthermore, HML-EV/liposomes can inhibit the synthesis of protease-activated receptor-2, interleukin-6, c-Jun, and thymic stromal lymphopoietin, thus exhibiting anti-inflammatory performance. These findings highlight that the hybrid EV/liposome system established in this study alleviates skin irritation and improves skin anti-inflammation.