Engineered reconstructed extracellular vesicles coloaded with Astragaloside IV/Paeoniflorin improve cerebral ischemia/reperfusion injurybyinhibiting the inflammatory response.

The method of nourishing qi and activating blood circulation is a key approach in traditional Chinese medicine for treating stroke. The combination of Astragaloside IV (qi-nourishing) and Paeoniflorin (blood-activating) in the BuYang HuanWu Decoction can enhance its therapeutic effects. Extracellular vesicles offer several advantages, including low immunogenicity, biodegradability, and the ability to cross the blood-brain barrier, making them ideal carriers for drug delivery. In this study, astragaloside IV and paeoniflorin were co-loaded into extracellular vesicles derived from milk using ultrasound, and RVG29 peptide was modified on their surface through hydrophobic insertion to achieve targeted delivery to the brain lesion area. Cell and small animal imaging experiments confirmed that these engineered reconstructed extracellular vesicles possess excellent brain-targeting capabilities. In the mouse model of cerebral artery occlusion/reperfusion, this co-delivery system significantly suppressed inflammation and improved brain injury, providing a new strategy for treating cerebral ischemia and demonstrating promising application prospects.