Chitosan nanoparticle encapsulation improves the effect of donepezil on impaired memory in an amnesia mouse model

Amnesia is one of the most important parts of Alzheimer’s disease (AD). Among the conventional and controlled drug delivery strategies for the pharmacological treatment of AD, nanotechnology-based systems targeting pharmacologically active molecules near their site of action seem to be the most effective. So, this study aimed to investigate the nano-chitosan encapsulated Donepezil on impaired memory in a mouse model of AD. This study was conducted on 232 male NMRI mice (30–35 mg) and carried out in three phases to identify the optimal ethanol dose for amnesia induction; to evaluate the effect of donepezil alone and donepezil enclosed in chitosan nano-particles after ethanol-induced amnesia. The effect of treatment was evaluated in an inhibitory passive avoidance apparatus. The data was recorded and analyzed in GraphPad Prism software using ANOVA and Tukey post hoc test. p < 0.05 was considered as the first significant level. Intraperituneally (IP) injection of 0.25, 0.5, 0.75, or 1 mg/kg non-capsulated or chitosan-encapsulated donepezil significantly improved impaired memory compared to that of the controls. However, at doses of 0.25 and 0.5 mg/kg, nano-chitosan-encapsulated donepezil had significantly greater effects than non-encapsulated donepezil (p < 0.0001 and p < 0.05, respectively). Encapsulation could reduce the required dose to achieve the desired memory improvement effect. Further studies are required to understand the efficiency of nano-chitosan-encapsulated donepezil administered via different delivery routes and the underlying mechanism of its improved effect on impaired memory.