Focused ultrasound-mediated blood-brain barrier opening enhances delivery of Rg3 ginseng nanoparticles in a Parkinson's disease mouse model.

The blood-brain barrier (BBB) severely restricts the delivery of neuroprotective compounds to the brain, limiting therapeutic strategies for Parkinson's disease (PD). Ginsenoside Rg3, a bioactive component of ginseng, has demonstrated neuroprotective potential, but its efficacy is constrained by poor BBB permeability. Here, we evaluated focused ultrasound (FUS)-mediated BBB opening (FUS BBBO) to enhance delivery of Rg3-loaded nanoparticles in a rotenone-induced mouse model of PD. Localized FUS sonications were applied to induce transient BBB disruption, followed by intraperitoneal administration of FITC-labeled Rg3 nanoparticles. In vivo and Ex vivo fluorescence imaging confirmed a significant increase in brain accumulation of nanoparticles after FUS BBBO. While Rg3 nanoparticle treatment alone showed moderate increases in ATP levels and Complex I activity, FUS alone produced comparable trends with slightly higher recovery. The combination treatment with FUS-mediated BBBO demonstrated higher mean values (ATP: 0.27 ± 0.06; Complex I: 1.98 ± 0.41) compared to the PD group, along with improvements in motor performance. These findings suggest that FUS-BBBO may enhance the delivery of Rg3 nanoparticles to the brain and support mitochondrial function. Overall, the combination approach showed a trend toward improved outcomes; however, further studies are required to confirm these effects and establish therapeutic potential for solid statistical analysis.