title: Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats.
abstract: It is essential to determine the biodistribution, clearance, and biocompatibility of magnetic nanoparticles (MNPs) for in vivo biomedical applications to ensure their safe clinical use. We have studied these aspects with our novel iron oxide MNP formulation, which can be used as a magnetic resonance imaging (MRI) agent and a drug carrier system. Changes in serum and tissue iron levels were analyzed over 3 weeks after intravenous administration of MNPs to rats. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) levels, and total iron-binding capacity (TIBC) were also measured with time to assess the effect of MNPs on liver function. Selected tissues were also analyzed for oxidative stress and studied histologically to determine biocompatibility of MNPs. Serum iron levels gradually increased for up to 1 week but levels slowly declined thereafter. Biodistribution of iron in various body tissues changed with time but greater fraction of the injected iron localized in the liver and spleen than in the brain, heart, kidney, and lung. Magnetization measurements of the liver and spleen samples showed a steady decrease over 3 weeks, suggesting particle degradation. Serum showed a transient increase in ALT, AST, AKP levels, and TIBC over a period of 6-24 h following MNP injection. The increase in oxidative stress was tissue dependent, reaching a peak at approximately 3 days and then slowly declining thereafter. Histological analyses of liver, spleen, and kidney samples collected at 1 and 7 days showed no apparent abnormal changes. In conclusion, our MNPs did not cause long-term changes in the liver enzyme levels or induce oxidative stress and thus can be safely used for drug delivery and imaging applications.
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Jain
authors.forename: Maram K
authors.initials: MK
authors.lastname: Reddy
authors.forename: Marco A
authors.initials: MA
authors.lastname: Morales
authors.forename: Diandra L
authors.initials: DL
authors.lastname: Leslie-Pelecky
authors.forename: Vinod
authors.initials: V
authors.lastname: Labhasetwar
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004337:Drug Carriers; D005290:Ferric Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D007501:Iron / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D053758:Nanoparticles; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; D007501:Iron; D000410:Alanine Transaminase