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Int. J. Mol. Sci. 2018, 19(1), 205; https://doi.org/10.3390/ijms19010205

Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration

1
Key Centre for Polymers and Colloids, School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia
2
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, NSW 2065, Australia
3
Sydney Medical School—Northern, University of Sydney, Sydney, NSW 2006, Australia
4
Sydney School of Veterinary Science, University of Sydney Teaching Hospital Camden, Camden, NSW 2570, Australia
5
Sirtex Medical Limited, North Sydney, NSW 2060, Australia
Binh T. T. Pham and Emily K. Colvin contributed equally, Viive M. Howell and Brian S. Hawkett contributed equally.
Current address: Barry H. Rickman, Sound VetPath, Edmonds, WA 98020, USA; Nicole S. Bryce, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
*
Authors to whom correspondence should be addressed.
Received: 12 September 2017 / Revised: 17 December 2017 / Accepted: 27 December 2017 / Published: 10 January 2018
(This article belongs to the Special Issue Nanotechnology in Drug Delivery)
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Abstract

Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent. View Full-Text
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Pham, B.T.T.; Colvin, E.K.; Pham, N.T.H.; Kim, B.J.; Fuller, E.S.; Moon, E.A.; Barbey, R.; Yuen, S.; Rickman, B.H.; Bryce, N.S.; Bickley, S.; Tanudji, M.; Jones, S.K.; Howell, V.M.; Hawkett, B.S. Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration. Int. J. Mol. Sci. 2018, 19, 205.

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