Intravenous Administration of Scutellarin Nanoparticles Augments the Protective Effect against Cerebral Ischemia–Reperfusion Injury in Rats

[Image: see text] This study investigates the protective effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with scutellarin (SCU), a flavone isolated from the traditional Chinese medicineErigeron breviscapus (Vant.) Hand.-Mazz., in reducing cerebral ischemia/reperfusion (I/R) injury in vivo. The focal cerebral I/R injury model was established by occluding the middle cerebral artery for 1 h in male Sprague-Dawley (SD) rats. Our SCU-PLGA NPs exhibited an extended in vitro release profile and prolonged blood circulation in rats with cerebral ischemia. More importantly, when administered intravenously once a day for 3 days, SCU-PLGA NPs increased the SCU level in the ischemic brain, compared to free SCU, resulting in a significant reduction of the cerebral infarct volume after cerebral I/R. Furthermore, SCU-PLGA NPs reversed the histopathological changes caused by cerebral I/R injury, as well as attenuated cell apoptosis in the brain tissue, as confirmed by hematoxylin and eosin, and TUNEL staining. Our findings have revealed that our injectable SCU-PLGA NPs provide promising protective effects against cerebral I/R injury, which could be used in combination with the existing conventional thrombolytic therapies to improve stroke management.