title: Biodistribution and pharmacokinetics of uniform magnetite nanoparticles chemically modified with polyethylene glycol.
abstract: The influence of polyethylene glycol (PEG) grafting on the pharmacokinetics, biodistribution and elimination of iron oxide nanoparticles is studied in this work. Magnetite nanoparticles (12 nm) were obtained via thermal decomposition of an iron coordination complex as a precursor. Particles were coated with meso-2,3-dimercaptosuccinic acid (DMSA) and conjugated to PEG-derived molecules by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC) chemistry. Using a rat model, we explored the nanoparticle biodistribution pattern in blood and in different organs (liver, spleen and lungs) after intravenous administration of the product. The time of residence in blood was measured from the evolution of water proton relaxivities with time and Fe analysis in blood samples. The results showed that the residence time was doubled for PEG coated nanoparticles and consequently particle accumulation in liver and spleen was reduced. Post-mortem histological analyses showed no alterations in the liver and confirm heterogeneous distribution of NPs in the organ, in agreement with magnetic measurements and iron analysis. Finally, by successive magnetic resonance images we studied the evolution of contrast in the liver and measured the absorption, time of residence and excretion of nanoparticles in the liver during a one month period. On the basis of these results we propose different metabolic routes that determine the fate of magnetic nanoparticles.
authors.affiliation: Departamento de Biomateriales y Materiales Bioinspirados, Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain. amaliaruiz@icmm.csic.es sabino@icmm.csic.es puerto@icmm.csic.es.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
authors.forename: Y
authors.initials: Y
authors.lastname: Hernández
authors.forename: C
authors.initials: C
authors.lastname: Cabal
authors.forename: E
authors.initials: E
authors.lastname: González
authors.forename: S
authors.initials: S
authors.lastname: Veintemillas-Verdaguer
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.forename: M P
authors.initials: MP
authors.lastname: Morales
mesh_terms: D000818:Animals; D002234:Carbodiimides / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: C557098:1-ethyl-3-(3-dimethylaminoisopropyl) carbodiimide; D002234:Carbodiimides; D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols; D004113:Succimer