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

Abstract

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 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

Acknowledgment

This work was supported by a grant from the Student Research Committee, Deputy of Research and Technology (9604029), Babol University of Medical Sciences, Babol, Iran.

Abbreviations

WHO, World Health Organization; ROS, reactive oxygen species; PTZ, pentylenetetrazole; BBB, blood–brain barrier; NPs, nanoparticles; MNPs, magnetic NPs; SPIONs, superparamagnetic iron oxide NPs; CD, cyclodextrin; DI, deionized water; FTIR, Fourier-transform infrared spectroscopy; IP, intraperitoneally; MJ, myoclonic jerk; GTCS, generalized tonic–clonic seizure; iNOS, inducible nitric oxide synthase.

Disclosure

The authors report no conflicts of interest in this work.