Chitosan nanoparticle-mediated nose-to-brain delivery of naringenin: Attenuating memory decline in experimental animals via behavioural assessment and modulation of biochemical parameters.

Naringenin, a flavonoid with potent antioxidant properties, faces low bioavailability, limiting its clinical application in Alzheimer's disease. This study developed naringenin-loaded chitosan nanoparticles (NAR-CNPs) for nose-to-brain delivery using the ionic gelation method. The NAR-CNPs exhibited an average particle size of 112.35 ± 1.55 nm, zeta potential of 15.36 ± 2.05 mV, and entrapment efficiency of 69.49 ± 1.88 %, with a sustained release profile (65.80 % over 8 h). Ex vivo permeation studies showed a 1.91-fold higher steady-state flux for NAR-CNPs compared to naringenin suspension, indicating enhanced brain penetration. The NAR-CNPs were safe for goat nasal mucosa and improved cognitive function in scopolamine-induced demented mice, whereas significantly reducing acetylcholinesterase activity (p < 0.001) and increasing antioxidant enzyme activities in the brain of experimental mice. Concurrently, the level of malondialdehyde was decreased in the brain, indicating reduced lipid peroxidation. Histopathological analysis showed a significant increase in neuronal count in NAR-CNPs treated animals compared to control group. These findings suggest that intranasally administered NAR-CNPs hold promise for treating cognitive impairment, though further studies are needed for clinical translation.