Fabrication of ethosuximide loaded alginate/polyethylene oxide scaffolds for epilepsy research using 3D-printing method

Hatice Karabulut; Abir Dutta; Yunis Moukbil; Aysim Cisen Akyol; Songul Ulag; Banu Aydin; Rezzan Gulhan; Zeynep Us; Deepak M Kalaskar; Oguzhan Gunduz

doi:10.3389/fbioe.2023.1244323

Fabrication of ethosuximide loaded alginate/polyethylene oxide scaffolds for epilepsy research using 3D-printing method

Front Bioeng Biotechnol. 2023 Dec 1:11:1244323. doi: 10.3389/fbioe.2023.1244323. eCollection 2023.

Authors

Hatice Karabulut^{1

2}, Abir Dutta³, Yunis Moukbil^{2

4}, Aysim Cisen Akyol^{2

5}, Songul Ulag^{2

6}, Banu Aydin⁷, Rezzan Gulhan^{8

9}, Zeynep Us⁸, Deepak M Kalaskar³, Oguzhan Gunduz^{2

6}

Affiliations

¹ Department of Systems Science and Industrial Engineering, State University of New York at Binghamton, Binghamton, NY, United States.
² Center for Nanotechnology and Biomaterials Application and Research, Marmara University, Istanbul, Türkiye.
³ UCL Division of Surgery and Interventional Sciences, Royal Free Hospital Campus, London, United Kingdom.
⁴ School of Medicine and Psychology, College of Health and Medicine, Australian National University, Canberra, ACT, Australia.
⁵ Department of Bioengineering, Graduate School of Natural and Applied Sciences, Yildiz Technical University, Istanbul, Türkiye.
⁶ Department of Metallurgy and Materials Engineering, Faculty of Technology, Marmara University, Istanbul, Türkiye.
⁷ Department of Biophysics, School of Medicine, Marmara University, Istanbul, Türkiye.
⁸ Department of Medical Pharmacology, School of Medicine, Marmara University, Istanbul, Türkiye.
⁹ Epilepsy Research and Implementation Center, Marmara University, Istanbul, Türkiye.

Abstract

Epilepsy is a medical condition that causes seizures and impairs the mental and physical activities of patients. Unfortunately, over one-third of patients do not receive adequate relief from oral Antiepileptic Drugs (AEDs) and continue to experience seizures. In addition to that, long term usage of Antiepileptic Drugs can cause a range of side effects. To overcome this problem, the precision of 3D printing technology is combined with the controlled release capabilities of biodegradable polymers, allowing for tailored and localized AED delivery to specific seizure sites. As a result of this novel technique, therapeutic outcomes can be enhanced, side effects of AEDs are minimized, and patient-specific dosage forms can be created. This study focused on the use of ethosuximide, an antiepileptic drug, at different concentrations (10, 13, and 15 mg) loaded into 3D-printed sodium alginate and polyethylene oxide scaffolds. The scaffolds contained varying concentrations (0.25%, 0.50%, and 0.75% w/v) and had varying pores created by 3D patterning sizes from 159.86 ± 19.9 µm to 240.29 ± 10.7 µm to optimize the releasing system for an intracranial administration. The addition of PEO changed the T_g and T_m temperatures from 65°C to 69°C and from 262°C to 267°C, respectively. Cytotoxicity assays using the human neuroblastoma cell line (SH-SY5Y) showed that cell metabolic activity reached 130% after 168 h, allowing the cells to develop into mature neural cells. In vitro testing demonstrated sustained ethosuximide release lasting 2 hours despite crosslinking with 3% CaCl₂. The workpaves the way for the use of ethosuximide -loaded scaffolds for treating epilepsy.

Keywords: 3D-printing; drug resistant epilepsy; epilepsy treatment; implantable scaffolds; polyethylene oxide; sodium alginate.

Grants and funding

TUBITAK (Project No. 23AG008) supported this work financially.