Abstract
Cerium oxide nanoparticles are a unique antioxidant mimicking the activity of natural antioxidant enzymes. Previous research showed its’ promising effect mitigating free radical damage in neurodegenerative disorders. However, there is still unmet therapeutic needs due to poor BBB penetration, a high accumulation in liver, kidney and spleen. This study aimed to synthesize and optimize nanoceria stabilized by natural bioactive polymers suitable for intranasal administration to manage multiple sclerosis. Among the different employed biopolymers, pectin-stabilized nanoceria exhibited the ideal properties with small particles size 87.20±3.43nm, high zeta potential -56.37±2.39mV and high free radical scavenging activity 85.27±0.07%. Then coating was achieved for the first time by two biopolymers: lactoferrin and chitosan producing a double coated cationic nanoceria. Biological assessment involved using experimental autoimmune encephalomyelitis animal model treated in a dose of 1mg/kg nanoceria for 15 days. Motor function testing in rats revealed 6- and 17-folds increase in latency time in rotating rod and hanging wire tests, respectively. Biochemical analysis revealed significant reduction in lipid peroxidation along with about 1-fold upgrading of the intrinsic antioxidant system. Moreover, histologic examination disclosed decreased degeneration of the brain and spinal cord of treated rats and much decreased liver toxicity.
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