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

Authors Lopalco A, Ali H, Denora N, Rytting E

Received 14 November 2014

Accepted for publication 18 January 2015

Published 11 March 2015 Volume 2015:10(1) Pages 1985—1996

DOI https://doi.org/10.2147/IJN.S77498

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Antonio Lopalco,1–3,* Hazem Ali,1,* Nunzio Denora,3 Erik Rytting1,4,5

1Department of Obstretrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA; 3Department of Pharmacy – Drug Sciences, University of Bari Aldo Moro, Bari, Italy; 4Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX, USA; 5Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA

*These authors contributed equally to this work

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 (Pe) 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

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