Fabrication and evaluation of novel quercetin-conjugated Fe3O4–β-cyclodextrin nanoparticles for potential use in epilepsy disorder

Abstract

Mona Hashemian,1 Maryam Ghasemi-Kasman,2,3 Shahram Ghasemi,4 Atefeh Akbari,5 Monire Moalem-Banhangi,1 Leila Zare,3 Seyed Raheleh Ahmadian11Student Research Committee, Babol University of Medical Sciences, Babol, Iran; 2Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 3Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 4Faculty of Chemistry, University of Mazandaran, Babolsar, Iran; 5Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, IranBackground: 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 Fe3O4–β-cyclodextrin (βCD) 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 βCD 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 Fe3O4–βCD 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–Fe3O4–βCD NPs might be regarded as an ideal therapeutic approach in epilepsy disorder.Keywords: quercetin, Fe3O4 nanoparticles, anticonvulsant, neuroprotection, astrocyte activation

Keywords

• Quercetin
• Fe3O4 nanoparticles
• Anticonvulsant
• Neuroprotection
• Astrocytes activation