title: Pharmacokinetics and bio-distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig.
abstract: Manufactured nanomaterials have a variety of medical applications, including diagnosis and targeted treatment of cancer. A series of experiments were conducted to determine the pharmacokinetic, biodistribution and biocompatibility of two novel magnetic nanoparticles (MNPs) in the anaesthetized pig. Dimercaptosuccinic acid (DMSA) coated superparamagnetic iron oxide nanoparticles (MF66-labelled 12 nm, core nominal diameter and OD15 15 nm); at 0.5, or 2.0 mg/kg) were injected intravenously. Particles induced a dose-dependent decrease in blood pressure following administration which recovered to control levels several minutes after injection. Blood samples were collected for a 5-h period and stored for determination of particle concentration using particle electron paramagnetic resonance (pEPR). Organs were harvested post-mortem for magnetic resonance imaging (MRI at 1.5 T field strength) and histology. OD15 (2.0 mg/kg) MNP had a plasma half-life of approximately 15 min. Both doses of the MF66 (0.5 and 2.0 mg/kg) MNP were below detection limits. MNP accumulation was observed primarily in the liver and spleen with MRI scans which was confirmed by histology. MRI also showed that both MNPs were present in the lungs. The results show that further modifications may be required to improve the biocompatibility of these particles for use as diagnostic and therapeutic agents.
authors.affiliation: Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Edge
authors.affiliation: Department of Physiology, University College Cork, Cork, Ireland.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Shortt
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Dublin, Ireland.
authors.forename: Oliviero L
authors.initials: OL
authors.lastname: Gobbo
authors.affiliation: PEPRIC nv, Leuven, Belgium.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Teughels
authors.affiliation: School of Medicine, Trinity College Dublin, Dublin, Ireland.|CRANN, Trinity College Dublin, Dublin, Ireland.
authors.forename: Adriele
authors.initials: A
authors.lastname: Prina-Mello
authors.affiliation: School of Medicine, Trinity College Dublin, Dublin, Ireland.|CRANN, Trinity College Dublin, Dublin, Ireland.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.affiliation: Mercy University Hospital, Dublin, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: MacEneaney
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Dublin, Ireland.
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
authors.affiliation: Department of Physiology, University College Cork, Cork, Ireland.
authors.forename: Farouk
authors.initials: F
authors.lastname: Markos
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005290:Ferric Compounds / Q000009:adverse effects / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D059346:Magnets; D010316:Particle Size; D013552:Swine; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide
keywords: biodistribution; blood pressure; electron paramagnetic resonance (pEPR); magnetic nanoparticles; magnetic resonance imaging (MRI)