Novel lactoferrin-functionalized manganese-doped silica hollow mesoporous nanoparticles loaded with resveratrol for the treatment of ischemic stroke

Stroke is a central nervous system disease with a high incidence at present. It can cause pathological changes such as oxidative stress, inflammation, neuronal apoptosis, and lead to disturbance of consciousness, disability, and even death. Due to the existence of the blood-brain barrier (BBB), most of the drugs cannot reach the lesions and exert their efficacy fully. Therefore, the purpose of this research was to design a lactoferrin functionalized hollow mesoporous manganese doped silica nanoparticles (LHMMSN) for delivery of insoluble drug resveratrol (RES). The system could help insoluble drugs pass through the BBB and target inflammatory sites to exert the antioxidant stress, anti-inflammatory and neuroprotective effects. The RES was adsorbed into LHMMSN with a particle size of about 140 nm by adsorption method, and the drug loading reached 39.32 ± 2.46%. In vitro and in vivo experiments showed that LHMMSN-RES could increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce brain reactive oxygen species (ROS) and malondialdehyde (MDA) content, increase the expression of anti-inflammatory factors (IL-10) and anti-apoptotic factors (bcl-2) in brain tissue, and reduce brain tissue pro-inflammatory factors (TNF-α, IL-1β, IL-6) and pro-apoptotic factors (BAX, Cleaved caspase-3) expression. In summary, LHMMSN-RES can reduce inflammation and protect nerve cells by inhibiting oxidative stress, thereby promoting the recovery of motor function in middle cerebral artery occlusion (MCAO) model rats.