Oxcarbazepine-loaded polymeric nanoparticles

Development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast

Antonio Lopalco, Hazem Ali, Nunzio Denora, Erik Rytting

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Encapsulation of antiepileptic drugs (AEDs) into nano particles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the trans-placental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nano particles 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<sup>®</sup> RGPd5055]). The physical properties of the developed nano particles 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 nano particles with encapsulation effciency 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 nano encapsulated drug. The apparent permeability (P<inf>e</inf>) values of the free and nano encapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nano particles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nano particles. Future developments in enzyme-pro drug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy.

Original languageEnglish (US)
Pages (from-to)1985-1996
Number of pages12
JournalInternational Journal of Nanomedicine
Volume10
DOIs
StatePublished - Mar 11 2015

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Trophoblasts
Encapsulation
Nanoparticles
Permeability
Surface active agents
Drug therapy
Surface-Active Agents
Anticonvulsants
Acids
Polydispersity
Zeta potential
Differential scanning calorimetry
Epilepsy
Brain
Enzymes
Physical properties
Prodrugs
X ray diffraction
Pharmaceutical Preparations
Kinetics

Keywords

  • BeWo cells
  • Coumarin-6
  • Epilepsy
  • HCMEC/D3 cells
  • Nanoparticles
  • PLGA

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

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abstract = "Encapsulation of antiepileptic drugs (AEDs) into nano particles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the trans-placental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nano particles 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{\circledR} RGPd5055]). The physical properties of the developed nano particles 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 nano particles with encapsulation effciency 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 nano encapsulated drug. The apparent permeability (Pe) values of the free and nano encapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nano particles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nano particles. Future developments in enzyme-pro drug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy.",
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