Niosome-encapsulated sodium butyrate enhances blood-brain barrier integrity and reduces neuroinflammation in a rat model of ischemic stroke

Ischemic stroke remains a major cause of mortality and disability worldwide, accompanied by severe inflammation and blood-brain barrier (BBB) disruption. Sodium butyrate (SB), a promising therapeutic agent, has been extensively studied for its anti-inflammatory effects in neurological disorders. However, its bioavailability is limited by low bioavailability and a short half-life. To address this challenge, SB-loaded niosome nanoparticles (NSB) were synthesized using the thin-film hydration method with a 1:1 ratio of Tween-60 and cholesterol and tested for physicochemical properties. NSB exhibited a particle size of 81.59 nm, PDI of 0.276, zeta potential of -3.36 mV, entrapment efficiency of 94.11 %, and 62.7 % reduction in cumulative release over 24 h. Also, Field-emission scanning electron microscopy (FE-SEM) confirmed the spherical morphology and polydispersity of the nanoparticles. To investigate the therapeutic efficacy of NSB, male Wistar rats were divided into four groups: sham, control, SB, and NSB. Treatments were administered intraperitoneally, followed by middle cerebral artery occlusion (MCAO). Neurobehavioral assessments, histopathological alterations, BBB permeability, biochemical factors, and relative mRNA expression of Tnf-α, Il-1β, Claudin-5, Zo-1, and Mmp-9 were measured 24 h post-reperfusion. NSB administration significantly reduced infarct volume, neurobehavioral deficits, BBB permeability, and histopathological damage compared to free SB. Additionally, NSB increased the enzyme activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde levels and mRNA expression of proinflammatory cytokines. Furthermore, NSB preserved BBB integrity by reducing Mmp-9 expression while upregulating Claudin-5 and Zo-1. These findings suggest niosomes as a promising nano-formulation to enhance SB bioavailability and neuroprotective efficacy in ischemic stroke.