Kandil_2021_Drug.Dev.Ind.Pharm__1

Alzheimer's disease is a common cause of dementia in the elderly. Galantamine hydrobromide (GH) is an anti-Alzheimer cholinesterase inhibitor that has an intrinsic antioxidant effect. In a previous study, GH was complexed with chitosan to prepare intranasal GH/chitosan complex nanoparticles (CX-NP2). The nanoparticles were located in rat brains 1 h after nasal administration and showed pharmacological superiority to GH nasal solution without showing histopathological toxicity. Objective: This study aimed to investigate whether the long-term administration of CX-NP2 leads to biochemical toxicity in rat brains compared to GH nasal solution. Methods: CX-NP2 dispersion and GH solution were administrated intranasally to male Wistar rats for 30 days (3 mg/kg/day). Malondialdehyde(MDA), lipid peroxidation marker, glutathione (GSH), superoxide dismutase (SOD) activity and tumor necrosis factor-alpha (TNF-alpha) were assessed in the brain extracts in all groups. Results: There was statistically insignificant difference between the CX-NP2 and GH nasal solution treated groups in all biochemical toxicity parameters assessed. Interestingly, MDA and TNF-alpha levels in CX-NP2-treated group significantly decreased compared to the control group. Also, GSH level and SOD activity were significantly enhanced in CX-NP2 treated group compared to the control group. Conclusions: CX-NP2 did not induce a statistically significant oxidative stress or neuroinflammation in rat brains after 30-day treatment, they rather elicited neuroprotective potentials.HighlightsIntranasal GH/chitosan complex nanoparticles (CX-NP2) show promising potential as a brain targeting carrier.Compared to GH nasal solution, nasal CX-NP2 formulation did not exert oxidative stress nor neuroinflammation when administered for 30 days.