Platelet Membrane-Encapsulated Ginkgolide B Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

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).

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

“…Since then, there has been a growing focus on platelet membrane-coated nanoparticles. For example, Cui et al selected GB, a neuroprotective agent with anti-inflammatory and antioxidant properties, and coated GB with platelet membranes (PM-GB) [216]. Because platelet membranes could target inflammatory injuries, the concentration of GB at the injury site increased, resulting in improved drug delivery to the lesion.…”