Fabrication and evaluation of novel quercetin-conjugated [Fe.sub.3][O.sub.4]--[beta]-cyclodextrin nanoparticles for potential use in epilepsy disorder

Background: Despite the numerous pharmacological activities of quercetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. In the present study, we fabricated a novel form of quercetin-conjugated [Fe.sub.3][O.sub.4]--[beta]-cyclodextrin ([beta]CD) nanoparticles (NPs), and the effect of these prepared NPs was evaluated in a chronic model of epilepsy. Methods: Quercetin-loaded NPs were prepared using an iron oxide core coated with [beta]CD and pluronic F68 polymer. The chronic model of epilepsy was developed by intraperitoneal injection of pentylenetetrazole (PTZ) at dose of 36.5 mg/kg every second day. Quercetin or its nanoformulation at doses of 25 or 50 mg/kg were administered intraperitoneally 10 days before PTZ injections and their applications continued 1 hour before each PTZ injection. Immunostaining was performed to evaluate the neuronal density and astrocyte activation of hippocampi. Results: Our data showed successful fabrication of quercetin onto [Fe.sub.3][O.sub.4]--[beta]CD NPs. In comparison to free quercetin, quercetin NPs markedly reduced seizure behavior, neuronal loss, and astrocyte activation in a PTZ-induced kindling model. Conclusion: Overall, quercetin--[Fe.sub.3][O.sub.4]--[beta]CD NPs might be regarded as an ideal therapeutic approach in epilepsy disorder. Keywords: quercetin, [Fe.sub.3][O.sub.4] nanoparticles, anticonvulsant, neuroprotection, astrocyte activation