Ethosuximide-loaded bismuth ferrite nanoparticles as a potential drug delivery system for the treatment of epilepsy disease
Yeliz Guldorum, Musa Ayran,Burcak Bulut, Sule Ilgar, Songul Ulag, Zehra Kanli, Banu Aydin, Rezzan Gulhan, Tuba Bedir, Oguzhan Gunduz, Roger J. Narayan
Abstract
Encapsulating antiepileptic drugs (AEDs), including ethosuximide (Etho), into nanoparticles shows promise in treating epilepsy. Nanomedicine may be the most significant contributor to addressing this issue. It presents several advantages compared to traditional drug delivery methods and is currently a prominent area of focus in cancer research. Incorporating Etho into bismuth ferrite (BFO) nanoparticles within diverse controlled drug delivery systems is explored to enhance drug efficacy. This approach is primarily desired to aid in targeted drug delivery to the brain’s deepest regions while limiting transplacental permeability, reducing fetal exposure, and mitigating associated adverse effects. In this investigation, we explored Etho, an antiepileptic drug commonly employed for treating absence seizures, as the active ingredient in BFO nanoparticles at varying concentrations (10 and 15 mg).
Introduction
Epilepsy, a widely prevalent neurological disorder worldwide, is primarily characterized by abnormal electrical activity in various brain regions. Neurodegeneration often results from excessive Ca2+ influx into neurons, causing cell death. Despite the availability of numerous antiseizure drugs, a substantial number of patients remain unresponsive to treatment, experiencing refractory epilepsy [1]. The fundamental approach in the treatment of epilepsy is to control the patient’s seizures by using the antiepileptic drug [2]. However, despite this medication successfully reducing or eliminating epileptic seizures in 70% of patients, it is ineffective in the remaining patients due to drug resistance [3].
Materials and method
Materials
Bismuth (III) nitrate pentahydrate [Bi(NO3)3•5H2O] was purchased from Merck (Darmstadt, Germany). Iron (III) nitrate nonahydrate [Fe(NO3)3.9H2O] was purchased from Merck (Darmstadt, Germany). Nitric acid (65%) was provided by Merck (Darmstadt, Germany). Ethosuximide was bought from Sigma Aldrich, USA.
Results
An investigation was conducted to examine how the presence of Etho affects the morphology of BFO nanoparticles, and it was subsequently observed that increasing the concentration of Etho led to changes in the BFO nanoparticles. Fig 1 depicts SEM images of BFO nanoparticles and Etho-reinforced BFO nanoparticles and their elemental analysis. The energy dispersive spectra obtained from SEM-EDS analysis for the nanoparticles provide clear evidence that the nanoparticles were synthesized using the aforementioned method. With regard to SEM visual inspection, variations in the homogeneous distribution of nanoparticle sizes among the different groups become apparent. Particularly, in the case of BFO images, the presence of larger nanoparticles is observed.
Conclusions
Epilepsy, a multifaceted and disabling neurological condition, afflicts millions globally, particularly impairing the quality of life in cases of uncontrolled seizures. The management of epilepsy involves a variety of drugs with diverse structures, each exerting its effects through distinct molecular mechanisms. In our study, all nanoparticles underwent assessments related to their morphology, thermal properties, and cytotoxicity. Additionally, the drug release characteristics of ethosuximide were investigated in a PBS solution. However, it was noted that as the concentration of Etho increased, the drug release duration increased up to 5 hours, suggesting a more controlled release profile.
Citation: Guldorum Y, Ayran M, Bulut B, Ilgar S, Ulag S, Kanli Z, et al. (2024) Ethosuximide-loaded bismuth ferrite nanoparticles as a potential drug delivery system for the treatment of epilepsy disease. PLoS ONE 19(9): e0305335. https://doi.org/10.1371/journal.pone.0305335
Editor: Nebojsa Bacanin, Univerzitet Singidunum, SERBIA
Received: November 15, 2023; Accepted: May 29, 2024; Published: September 23, 2024
Copyright: © 2024 Guldorum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript.
Funding: This study was financially supported by the Turkish Scientific and Technical Research Council (TUBITAK) (Project. No. 23AG008).
Competing interests: The authors have declared that no competing interests exist.
