Belete A., Metz H., Mueller T., Maeder K.
Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany; Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, Addis Ababa University, Churchill Road, Addis Ababa, Ethiopia; Medical Faculty, Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
Belete, A., Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany, Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, Addis Ababa University, Churchill Road, Addis Ababa, Ethiopia; Metz, H., Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany; Mueller, T., Medical Faculty, Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany; Maeder, K., Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
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 ∼13.5nm hydrophobic oleic acid stabilized monodisperse magnetite nanocrystals core and lipid-based amphiphilic stabilizers were performed using a prototype benchtop MR imager (22MHz) and pulsed nuclear magnetic resonance (NMR) system (20MHz), 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. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
amphophile; cremophor; macrogol 2000; magnetite nanocrystal; nanocrystal; nuclear magnetic resonance imaging agent; oleic acid; phosphatidylcholine; phosphatidylethanolamine; stabilizing agent; sucrose ester derivative; superparamagnetic iron oxide nanoparticle; unclassified drug; magnetite nanoparticle; oleic acid; water; animal experiment; animal tissue; aqueous solution; Article; controlled study; drug distribution; drug efficacy; drug formulation; drug half life; drug safety; ex vivo study; female; hydrophobicity; in vivo study; liver clearance; mouse; nonhuman; nuclear magnetic resonance imaging; quantitative analysis; tissue distribution; animal; Bagg albino mouse; chemistry; drug effects; drug screening; medicinal chemistry; metabolism; nuclear magnetic resonance imaging; physiology; procedures; Animals; Chemistry, Pharmaceutical; Drug Evaluation, Preclinical; Female; Magnetic Resonance Imaging; Magnetite Nanoparticles; Mice; Mice, Inbred BALB C; Oleic Acid; Tissue Distribution; Water