Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.
OBJECTIVE
We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance.


METHODS
The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver.


RESULTS
After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch.


CONCLUSIONS
The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.
Briley-Saebo
Karen C
KC
Imaging Science Laboratories, Mount Sinai School of Medicine, New York, NY 10029, USA. k_saeboe@yahoo.com
Johansson
Lars O
LO
Hustvedt
Svein Olaf
SO
Haldorsen
Anita G
AG
Bjørnerud
Atle
A
Fayad
Zahi A
ZA
Ahlstrom
Haakan K
HK
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D010087:Oxides / Q000493:pharmacokinetics*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide