Lipid-coated mesoporous silica nanoparticles loaded with Thymoquinone as a novel treatment for experimental autoimmune encephalomyelitis in rats.

AIMS: Crossing the blood-brain barrier (BBB) remains a significant challenge for delivering therapeutic agents to the central nervous system. This study aimed to evaluate the potential of a novel nanoformulation-mesoporous silica nanoparticles (MSN) coated with a lipid bilayer (LB)-to enhance the delivery and potential remyelinating effects of Thymoquinone (TQ). METHODS: The formulations were characterized by transmission electron microscopy and dynamic light scattering for zeta potential and particle size determination. The experimental autoimmune encephalomyelitis (EAE) model is used as an established animal model for multiple sclerosis (MS). Our experiment consists of five groups of male Wistar rats: a standard control group, an EAE-induced group, and three treated groups after being induced with EAE: (Thymoquinone) TQ-treated group (60 mg/kg TQ), MSN-treated group (60 mg/kg MSN), and LB-MSN-treated group (60 mg/kg MSN loaded with TQ and coated with lipid bilayer). KEY FINDINGS: The LB-MSN formulation was associated with a modulation of oxidative stress markers in specific brain areas. Notable increases in reduced glutathione were observed in the cortex (26.53%) and hippocampus (22.82%), alongside a modest increase in catalase in the medulla (7.90%). These biochemical changes correlated with improvements in exploratory behavior in the open field test. Furthermore, neuropathological assessment of various brain regions and sciatic nerves revealed evidence of axonal remyelination in treated groups. SIGNIFICANCE: The findings suggest that the LB-MSN formulation may enhance the delivery and therapeutic profile of TQ, primarily through its association with anti-inflammatory and remyelinating effects. CONCLUSION: LB-MSN shows potential as a drug delivery system for the management of EAE.