Briley-Saebo Karen C, Johansson Lars O, Hustvedt Svein Olaf, Haldorsen Anita G, Bjørnerud Atle, Fayad Zahi A, Ahlstrom Haakan K
Imaging Science Laboratories, Mount Sinai School of Medicine, New York, NY 10029, USA.
Invest Radiol. 2006 Jul;41(7):560-71. doi: 10.1097/01.rli.0000221321.90261.09.
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.
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.
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.
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.
我们试图评估各种氧化铁制剂的粒径和包衣材料对大鼠肝脏清除率的影响。
本研究使用了以下氧化铁制剂：葡聚糖包被的铁氧化物（粒径 = 97 nm）和铁葡聚糖-10（粒径 = 21 nm）、羧基葡聚糖包被的SHU555A（粒径 = 69 nm）和分级的SHU555A（粒径 = 12 nm），以及氧化淀粉包被的材料，未配制的NC100150（粒径 = 15 nm）或配制的NC100150注射液（粒径 = 12 nm）。所有制剂均以2种剂量水平给予165只大鼠。在63天的时间段内获取肝脏定量R2*值。通过弛豫测量法测定肝脏中氧化铁颗粒的浓度，并使用这些值计算颗粒在肝脏中的半衰期。
给予高剂量氧化铁后，葡聚糖包被材料在大鼠肝脏中氧化铁颗粒的半衰期为8天，羧基葡聚糖材料为10天，未配制的氧化淀粉为14天，配制的氧化淀粉为29天。
研究结果表明，具有相似包衣但不同粒径的材料表现出相似的肝脏清除率。因此，得出结论：包衣材料显著影响大鼠肝脏中氧化铁的清除率。
