Exosome-mediated scutellarin delivery enhances BBB penetration and microglia targeting in antiviral neuroprotection

Scutellarin, the active component of Erigeron breviscapus(Vant.)Hand.-Mazz, has therapeutic potential for neurological diseases but is limited by poor solubility, low bioavailability, and inability to cross the blood-brain barrier (BBB). This study used mouse brain tissue-derived exosomes as a delivery system for scutellarin. Exosomes were isolated via ultracentrifugation and loaded with scutellarin using ultrasonication, achieving a drug loading capacity of 31.86 ng/μg and a particle size of 90-120 nm. In an in vitro BBB model, exosome-loaded scutellarin showed significantly higher penetration (41 %) than the free drug (13.5 %). Confocal microscopy confirmed efficient cellular uptake, particularly by microglia (98 % efficiency). In vivo, exosomes accumulated and persisted in brain tissue for over 24 h. In a PRV-infected microglia model, exosome-delivered scutellarin significantly inhibited viral replication and modulated microglial polarization by downregulating the pro-inflammatory marker CD86 and upregulating the anti-inflammatory marker CD206. These findings demonstrate that brain-derived exosomes enhance scutellarin delivery across the BBB and improve its anti-neuroinflammatory effects, supporting their use as drug carriers for treating neuroinflammatory diseases.