BackgroundThe Blood-Brain Barrier (BBB), which protects the brain from many medications, is the biggest challenge for researchers testing new neurological treatments. Our research uses lipid bilayer-coated (LB) mesoporous silica nanoparticles (MSN) to increase gallic acid (GA) absorption over the BBB and improve its therapeutic benefits. MethodsThe formulations were characterized using Fourier transform infrared, x-ray diffraction (XRD), transmission electron microscopy, drug release, encapsulation efficiency, loading capacity, process yield, and dynamic light scattering to assess particle size and calculate zeta potential. Our investigation divided male Wistar rats into five groups: control, MSN, GA (20 mg/kg GA), MSN-GA, and LB-MSN-GA. HPLC biodistribution, oxidative stress, and cortical and hippocampal histopathology were also done. Key findingsThis study shows gallic acid can be encapsulated into MSN-GA and LB-MSN-GA nanoparticles with good loading capacities and encapsulation efficiency. Fourier transform infrared spectroscopy (FTIR) and XRD confirmed nanoparticle mesoporousness. The study also indicated that LB-MSN-GA may modify cortical and hippocampal histopathological and biochemical parameters. LB-MSN-GA loading altered GA distribution maps across the cortex and hippocampus. ConclusionGallic acid (GA) transfer via LB-MSN-GA substantially impacts rats' cortex and hippocampus. Therefore, one promising method of drug delivery for the brain is LB-MSN-GA.