title: Magnetic field enhanced convective diffusion of iron oxide nanoparticles in an osmotically disrupted cell culture model of the blood-brain barrier.
abstract: OBJECTIVE
  The present study examines the use of an external magnetic field in combination with the disruption of tight junctions to enhance the permeability of iron oxide nanoparticles (IONPs) across an in vitro model of the blood-brain barrier (BBB). The feasibility of such an approach, termed magnetic field enhanced convective diffusion (MFECD), along with the effect of IONP surface charge on permeability, was examined.
  
  
  METHODS
  The effect of magnetic field on the permeability of positively (aminosilane-coated [AmS]-IONPs) and negatively (N-(trimethoxysilylpropyl)ethylenediaminetriacetate [EDT]-IONPs) charged IONPs was evaluated in confluent monolayers of mouse brain endothelial cells under normal and osmotically disrupted conditions.
  
  
  RESULTS
  Neither IONP formulation was permeable across an intact cell monolayer. However, when tight junctions were disrupted using D-mannitol, flux of EDT-IONPs across the bEnd.3 monolayers was 28%, increasing to 44% when a magnetic field was present. In contrast, the permeability of AmS-IONPs after osmotic disruption was less than 5%. The cellular uptake profile of both IONPs was not altered by the presence of mannitol.
  
  
  CONCLUSIONS
  MFECD improved the permeability of EDT-IONPs through the paracellular route. The MFECD approach favors negatively charged IONPs that have low affinity for the brain endothelial cells and high colloidal stability. This suggests that MFECD may improve IONP-based drug delivery to the brain.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, OH, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Worden
authors.affiliation: Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Wroczynskyj
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Vinith
authors.initials: V
authors.lastname: Yathindranath
authors.affiliation: Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Johan
authors.initials: J
authors.lastname: van Lierop
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada ; Department of Chemistry and Biochemistry, Kent State University, Kent, OH, USA ; Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada ; Chemical Physics Interdisciplinary Program, Liquid Crystal Institute, Kent State University, Kent, OH, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Hegmann
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Miller
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry* / Q000528:radiation effects*; D002460:Cell Line; D018481:Convection; D004058:Diffusion / Q000528:radiation effects; D018274:Electroporation / Q000379:methods*; D042783:Endothelial Cells / Q000737:chemistry* / Q000528:radiation effects*; D055909:Magnetic Field Therapy / Q000379:methods; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000528:radiation effects*; D051379:Mice
chemical_list: D058185:Magnetite Nanoparticles
keywords: blood-brain barrier; drug delivery; iron oxide nanoparticles; magnetic targeting; permeability