Aluminum chloride (AlCl3) and its accumulation in the brain are associated with neurodegenerative disease. Recent investigations have illustrated that silibinin is known to have neuroprotective properties. The present study investigates the neuroprotective effects of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against AlCl3-induced neurotoxicity in male mice. Sili-NLCs were prepared using the emulsification-solvent evaporation method and subjected to particle size, zeta potential, and entrapment efficiency (% EE) analysis. Mice were treated with AlCl3 (100 mg/kg/day, p.o.) and with the same concentration of silibinin and Sili-NLCs (50,100, and 200 mg/kg/day, p.o.) for 30 days in different groups. After treating animals, behavioral studies were assessed. Also, the brain tissue samples were collected from all mice to evaluate oxidative damage and histological changes. The particle size, polydispersity index, zeta potential, and entrapment efficiency (% EE) of prepared Sili-NLCs found 239.7 ± 4.04 nm, 0.082 ± 0.003, - 16.33 ± 0.15 mV, and 72.65 ± 2.03 %, respectively. Brain uptake studies showed that Sili-NLCs had a 5.7-fold greater uptake in the mice brain than the free drug. The AlCl3 caused significant cognitive impairment and increased the level of lipid peroxidation accompanied by decreasing antioxidant enzyme activity in the brain tissue. These findings correlated well with the histopathological experiments. Furthermore, treatment with Sili-NLCs significantly improved the AlCl3-induced cognitive impairment, neurochemical anomalies, and histopathological changes. Given these results, silibinin, when delivered using NLCs, is potentially more effective than free silibinin in decreasing AlCl3- induced neurotoxicity.
Keywords: Aluminum chloride; Nanostructured lipid carriers; Oxidative stress; Silibinin.
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