title: Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.
abstract: BACKGROUND
  Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency.
  
  
  METHODS
  Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2g/kg) 1h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology.
  
  
  RESULTS
  Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48h for USPIO and MPIO, respectively.
  
  
  CONCLUSIONS
  Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles.
  
  
  CONCLUSIONS
  Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
authors: Li
authors: L
authors: Liu
authors: T Kevin
authors: TK
authors: Hitchens
authors: Qing
authors: Q
authors: Ye
authors: Yijen
authors: Y
authors: Wu
authors: Brent
authors: B
authors: Barbe
authors: Devin E
authors: DE
authors: Prior
authors: Wendy F
authors: WF
authors: Li
authors: Fang-Cheng
authors: FC
authors: Yeh
authors: Lesley M
authors: LM
authors: Foley
authors: Daniel J
authors: DJ
authors: Bain
authors: Chien
authors: C
authors: Ho
mesh_terms: D000818:Animals; D001682:Biological Availability; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000494:pharmacology; D004655:Emulsions / Q000493:pharmacokinetics / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics* / Q000494:pharmacology; D005290:Ferric Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D058185:Magnetite Nanoparticles; D008297:Male; D010743:Phospholipids / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D013024:Soybean Oil / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; C000499:ferric oxide; D013024:Soybean Oil
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