Energy dispersive X-ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice

Authors

  • Anil Patri,

    1. Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA
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  • Thomas Umbreit,

    Corresponding author
    1. Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
    • Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • J. Zheng,

    1. Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA
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  • K. Nagashima,

    1. Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA
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  • Peter Goering,

    1. Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • Sabine Francke-Carroll,

    1. Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, Maryland 20740, USA
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  • Edward Gordon,

    1. Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • James Weaver,

    1. Center for Drug Evaluation and Research, DAPR, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • Terry Miller,

    1. Center for Drug Evaluation and Research, DAPR, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • Nakissa Sadrieh,

    1. Center for Drug Evaluation and Research, DAPR, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • Scott McNeil,

    1. Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA
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  • Mel Stratmeyer

    1. Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland 20903, USA
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  • This article is a US Government work and is in the public domain in the USA.

Abstract

In an effort to understand the disposition and toxicokinetics of nanoscale materials, we used EDS (energy dispersive X-ray spectroscopy) to detect and map the distribution of titanium dioxide (TiO2) in tissue sections from mice following either subcutaneous (s.c.) or intravenous (i.v.) injection. TiO2 nanoparticles were administered at a dose of 560 mg/kg (i.v.) or 5600 mg/kg (s.c.) to Balb/c female mice on two consecutive days. Tissues (liver, kidney, lung, heart, spleen, and brain) were examined by light microscopy, TEM (transmission electron microscopy), SEM (scanning electron microscopy), and EDS following necropsy one day after treatment. Particle agglomerates were detected by light microsopy in all tissues examined, EDS microanalysis was used to confirm that these tissues contained elemental titanium and oxygen. The TEM micrographs and EDS spectra of the aggregates were compared with in vitro measurements of TiO2 nanoparticle injection solution (i.e., in water). The nanoparticles were also characterized using dynamic light scattering in water, 10 mM NaCl, and phosphate buffered saline (PBS). In low ionic strength solvents (water and 10 mM NaCl), the TiO2 particles had average hydrodynamic diameters ranging from 114–122 nm. In PBS, however, the average diameter increases to 1–2 μm, likely due to aggregation analogous to that observed in tissue by TEM and EDS. This investigation demonstrates the suitability of energy dispersive X-ray spectroscopy (EDS) for detection of nanoparticle aggregates in tissues and shows that disposition of TiO2 nanoparticles depends on the route of administration (i.v. or s.c.). Published in 2009 by John Wiley and Sons, Ltd.

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