Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast

Abstract

Encapsulation of antiepileptic drugs (AEDs) into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid) [PLGA] with or without surfactant and PEGylated PLGA [Resomer^® RGPd5055]). The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood–brain barrier (hCMEC/D3 cells) and human placental trophoblast cells (BeWo b30 cells). Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140–170 nm, polydispersity indices below 0.3, and zeta potential values below -34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (P_e) values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nanoparticles. Future developments in enzyme-prodrug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy.

Keywords:

• nanoparticles
• epilepsy
• PLGA
• BeWo cells
• coumarin-6
• hCMEC/D3 cells

Acknowledgments

The authors would like to thank Andrea Latrofa, Associate Professor at the University of Bari Aldo Moro, for his scientific contributions and professional discussions. Mark White and Michael Sherman from the Department of Biochemistry and Molecular Biology and the Sealy Center for Structural Biology and Molecular Biophysics at the University of Texas Medical Branch are thanked for their assistance with the X-ray diffraction and cryo-TEM experiments, respectively. This research was supported in part by the William and Mary McGanity Research Fund in Obstetrics and Gynecology and by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women’s Health Program, BIRCWH) from the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the Office of the Director (OD), National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID, NICHD, OD, or the National Institutes of Health.

Disclosure

The authors report no conflicts of interest.