effect of magnetic tacrine-loaded chitosan nanoparticles on spatial learning, memory, amyloid precursor protein and seladin-1 expression in the hippocampus of streptozotocin-exposed rats

alzheimer's disease (ad) is a progressive neurodegenerative disease characterized by memory and cognitive dysfunction due to neuronal cell loss in higher brain centers. senile plaques containing amyloid β (aβ) are associated with this disease as well as a reduction in cholinergic neuron numbers. tacrine is a reversible cholinesterase inhibitor in clinical use to treat moderate forms of ad. chitosan nanoparticles represent an effective systemic delivery system for drugs. the application of tacrine-loaded chitosan nanoparticles has been shown to selectively increase tacrine concentrations in the brain tissue. in this study, we compared magnetic and non-magnetic tacrine-loaded chitosan nanoparticles for their bioactivity and neuroprotective potency in streptozotocin (stz)-induced neurodegeneration, an accepted animal model for ad. male rats received a single injection of stz via an implanted cannula into the lateral brain ventricle. tacrine (tac)-loaded chitosan nanoparticles were delivered into the tail vein. spatial learning and memory were analyzed using the morris water maze task. amyloid precursor protein gene (app) and seladin-1 gene expression were studied in the hippocampus by real time-pcr. tac-loaded non-magnetic and tac-loaded magnetic chitosan nanoparticles improved spatial learning and memory after stz treatment with magnetic nanoparticles being most effective. similarly, tac-loaded chitosan nanoparticles increased seladin-1 and reduced app gene expression. again, magnetic nanoparticles were more effective. these data reveal that tac-loaded non magnetic and tac-loaded magnetic chitosan nanoparticles to a higher extent improve brain deficits related to stz application. we conclude that the magnetic target drug delivery system is a promising therapeutic strategy to protect ad-related degenerating in the cns.