Preparation, Characterization and Optimization of Repurposed Valproic Acid Loaded Carboxymethyl Chitosan Nanoparticles by Box–Behnken Design for Alzheimer Management

Aim/Background: Alzheimer’s disease (AD) is one of the most ominous diseases, leads dementia but highest unmet till today. The new strategy needed via repositioning due to the limitation of existing therapies. Valproic acid is one of the first line drugs for epilepsy and bipolar disorder showed neuroprotective potential by decreased Aβ production in AD. Methods: The objective of this research was to prepare the repurposed VPA loaded polymeric nanoparticles using carboxymethyl chitosan for management of AD through the intranasal route. Polymeric nanoparticle (PNPs) was prepared by ionic gelation method and optimization was done using Box-Behnken design (BBD) model. Results: Characterization of optimized PNPs was done for Particle size which was found to be 384± 1.45 nm with drug release of 82.39% ± 3.1 after 48 hr. In vitro cytotoxicity using cell line, SH-SY5Y and IC50 value of optimized formulation was found to be 42.96 μg/ml. Ex vivo histopathological study was performed using goat nasal mucosa for the Nasalcilio toxicity studies which showed no inflammation and toxicity for VPA-CMC PNPs and indicate the safe formulation. Conclusion: The outcome of the research is a positive direction to reuse the VPA for the management of AD in the near future through the intranasal route.