title: Superparamagnetic iron oxide nanoparticles stabilized by alginate: pharmacokinetics, tissue distribution, and applications in detecting liver cancers.
abstract: The objectives of this study were to describe the pharmacokinetics and tissue distribution of superparamagnetic iron oxide nanoparticle (SPIO) stabilized with alginate (SPIO-alginate), and investigate its potential in detecting liver cancers as a newly developed magnetic resonance (MR) contrast agent. Pharmacokinetics and tissue distribution of SPIO-alginate were investigated in Sprague-Dawley rats. The results showed that SPIO-alginate was eliminated rapidly from serum with the half-life of 0.27 h at 109.5 micromol Fe/kg and accumulated dominantly in liver and spleen with a total percentage of more than 90% of dose after intravenous injection. The studies of pharmacokinetics and distribution of SPIO-alginate in rats indicated the MR contrast agent, based on SPIO, mainly accumulating in targeting organs that contain phagocytosing cells, i.e. liver and spleen. The efficacies in detecting hepatocellular carcinoma (HCC) of rat with primary liver cancer and xenograft liver cancers of rabbit were investigated before and after injection of SPIO-alginate. The signal intensity of liver parenchyma in rabbit with VX2 tumor after injection of SPIO-alginate was reduced sharply resulting in a significant contrast between liver parenchyma and tumor. Detection of the HCC in rat model was also demonstrated. The present study provides evidence that SPIO-alginate might have the ability to improve the detection of liver tumors as an MR contrast agent, and the efficacy is associated with the SPIO specifically located in Kupffer cells in hepatic sinusoid.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
authors.forename: Hui Li
authors.initials: HL
authors.lastname: Ma
authors.forename: Yu Feng
authors.initials: YF
authors.lastname: Xu
authors.forename: Xian Rong
authors.initials: XR
authors.lastname: Qi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.forename: Tsuneji
authors.initials: T
authors.lastname: Nagai
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D020723:Glucuronic Acid / Q000737:chemistry; D006207:Half-Life; D006603:Hexuronic Acids / Q000737:chemistry; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053758:Nanoparticles; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000464:Alginates; D003287:Contrast Media; D005290:Ferric Compounds; D006603:Hexuronic Acids; C000499:ferric oxide; D020723:Glucuronic Acid