Baicalin-loaded macrophage-derived exosomes ameliorate ischemic brain injury via the antioxidative pathway.

Baicalin (BA), a strong free radical scavenger, has been demonstrated to exert neuroprotective effects in the treatment of ischemic stroke. However, its clinical application has been limited due to its inability to target the brain and its poor solubility. In this study, we designed novel brain-targeted BA-loaded macrophage-derived exosomes (Exo-BA) to induce neuroprotection against ischemic stroke in animal models. The results revealed that with the help of Exo, the solubility of BA was significantly enhanced. In addition, Exo-BA displayed better brain targeting ability than free BA, as they induced the transfer of more BA into the brain, in a transient middle cerebral artery occlusion/reperfusion (tMCAO) model and permanent middle cerebral artery occlusion (pMCAO) model. Compared with free BA, Exo-BA significantly reduced the generation of reactive oxygen species (ROS) and activated the Nrf2/HO-1 pathway in neurons, thus significantly alleviating cerebral ischemic injury in a stroke model.