title: Biodistribution of negatively charged iron oxide nanoparticles (IONPs) in mice and enhanced brain delivery using lysophosphatidic acid (LPA).
abstract: Effective treatment of brain disorders requires a focus on improving drug permeability across the blood-brain barrier (BBB). Herein, we examined the pharmacokinetic properties of negatively charged iron oxide nanoparticles (IONPs) and the capability of using lysophosphatidic acid (LPA) to transiently disrupt the tight junctions and allow IONPs to enter the brain. Under normal conditions, IONPs had a plasma half-life of six minutes, with the liver and spleen being the major organs of deposition. Treatment with LPA enhanced accumulation of IONPs in the brain and spleen (approximately 4-fold vs. control). LPA and IONP treated mice revealed no sign of peripheral immune cell infiltration in the brain and no significant activation of microglia or astrocytes. These studies show improved delivery efficiency of IONPs following LPA administration. Our findings suggest transient disruption of the BBB may be a safe and effective method for increasing IONP delivery to the brain.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, 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 Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Thliveris
authors.affiliation: Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hombach-Klonisch
authors.affiliation: Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.affiliation: Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Johan
authors.initials: J
authors.lastname: van Lierop
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada; Department of Chemistry and Biochemistry, Kent State University, Kent, OH, USA; 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, MB, Canada. Electronic address: donald.miller@umanitoba.ca.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Miller
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain; D005290:Ferric Compounds; D008246:Lysophospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles; D013154:Spleen; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D008246:Lysophospholipids; C000499:ferric oxide
keywords: BBB disruption; Biodistribution; Blood–brain barrier; Brain delivery; Iron oxide nanoparticles