Platelet Membrane-Encapsulated Ginkgolide B Biomimetic Nanoparticles for the Treatment of Ischemic Stroke
Jing-Wen Cui, Huicong Feng, Chang Xu, Dingyuan Jiang, Kaihua Zhang, Nana Gao, Yuan Wang, He Tian, Chang Liu
Abstract
Stroke is a highly lethal and disabling disease of the central nervous system exacerbated by oxidative stress, inflammation, and ferroptosis. However, the blood–brain barrier makes it extremely difficult for most medications to enter the brain, necessitating extremely high drug concentrations. Thus, we developed platelet-derived nanoparticles to deliver ginkgolide B (GB), a compound that has anti-inflammatory, antioxidative stress, and ferroptosis inhibition properties and assists acute stroke recovery. GB was encapsulated in a platelet membrane (PM) with a particle size of approximately 68.32 ± 3.7 nm, and the encapsulation efficiency reached 79.43 ± 6.3%. Experiments showed that PM-derived nanoparticles with GB (PM-GB) increased the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and decreased malondialdehyde(MDA) and reactive oxygen species(ROS) levels in the brain. Additionally, the PM-GB group had higher ferroptosis suppressor protein (GPX4, FSP1) expression, approximately 4-folds, with lower levels of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, and ferroptosis marker protein (PTGS2) compared with the OGD group. In conclusion, PM-GB reduces ferroptosis and inflammation by inhibiting oxidative stress, which protects neural cells and promotes motor recovery in middle cerebral artery occlusion model rats (MCAO/R).