title: Benchtop MRI for pharmacokinetic evaluation of two aqueous-based nano-scaled formulations of oleic acid stabilized magnetite nanocrystals.
abstract: BACKGROUND
  The interplay between numerous factors, including the size, shape, coating, surface charge and composition of particles is known to affect the pharmacokinetics and biodistribution of superparamagnetic iron oxides (SPIOs). This makes understanding the role of each factor independently quite challenging.
  
  
  METHODS
  In the present study, the in vivo magnetic resonance imaging (MRI), biodistribution and hepatic clearance evaluations of two SPIOs Formulations A and B developed from ∼13.5 nm hydrophobic oleic acid stabilized monodisperse magnetite nanocrystals core and lipid-based amphiphilic stabilizers were performed using a prototype benchtop MR imager (22 MHz) and pulsed nuclear magnetic resonance (NMR) system (20 MHz), respectively. Formulation A was composed of mPEG-2000-DSPE and Formulation B was composed of Phospholipon-100H, sucrose ester M-1695 and Cremophor RH-40.
  
  
  RESULTS
  The in vivo MRI investigations showed that both formulations were safe and effective as potential liver MR contrast agents with sustained liver contrast for at least seven days. In addition, ex vivo relaxometric investigations revealed that the formulations predominantly distribute to the liver and spleen following I.V. injection. The hepatic clearance kinetics determined based on the relaxometric quantification method indicated that both formulations exhibited a biphasic clearance process with a slow terminal clearance half-life of 11.5 and 12.7 days, respectively, for Formulations A and B.
  
  
  CONCLUSIONS
  The results of this study showed the potential biomedical applications of the investigated magnetopharmaceutical formulations as MRI contrast agents.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg , Halle (Saale) , Germany .
authors.forename: Anteneh
authors.initials: A
authors.lastname: Belete
authors.forename: Hendrik
authors.initials: H
authors.lastname: Metz
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: Karsten
authors.initials: K
authors.lastname: Maeder
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D019301:Oleic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014867:Water / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D058185:Magnetite Nanoparticles; D014867:Water; D019301:Oleic Acid
keywords: Benchtop MRI; MRI contrast agent; biodistribution; ex vivo relaxometry; hepatic clearance; magnetite nanocrystals