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Biodistribution, cellular localization, and in vivo tolerability of 35S-labeled antiinflammatory dendritic polyglycerol sulfate amine

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Abstract

Antiinflammatory dendritic polyglycerol sulfate (dPGS) holds great potential in the treatment and imaging of inflammatory processes. Here, we studied its biokinetic behavior, biodistribution, target cells, and in vivo toxicology. Following intravenous or subcutaneous application of 35sulfur-labeled dPGS amine with a molecular weight of 10.05 kDa and a hydrodynamic diameter of 5.7 ± 1.5 nm to mice, tissues were collected at specific time points (2, 15 min; 1, 24 h; 5, 21 days) and analyzed by liquid scintillation counting, autoradiography, radioluminography, and light microscopic autoradiography. The blood half-life of dPGS amine was 12 days. The major route of elimination was via the bile and feces. Elimination via the kidney and urine was only initially observed after i.v., but not after s.c. injection. Regardless of the administration mode, liver and spleen were late target organs where dPGS amine accumulated in phagocytic cells. Despite bioaccumulation, toxicological histopathology failed to identify any adverse effects at any time and in any tissues examined suggesting a high in vivo biocompatibility and encouraging future investigation for biomedical applications.

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Abbreviations

C max :

Maximum concentration

dPGS:

Dendritic polyglycerol sulfate

HE:

Hematoxylin and eosin

ID:

Injected dose

i.v.:

Intravenous

LMA:

Light microscopic autoradiography

LSC:

Liquid scintillation counting

MPS:

Mononuclear phagocyte system

NP:

Nanoparticle

p.a.:

Post administration

PSP:

Photostimulable phosphor plate

s.c.:

Subcutaneous

SD:

Standard deviation

SOA:

Single-organ autoradiography

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Acknowledgments

We thank Adelheid Hagenbach and Ulrich Abram for support by the Liquid Scintillation Counting technique and construction of radioactive dPG35S amine as well as Nancy A. Erickson for helpful discussions.

This work was supported by the Helmholtz Virtual Institute on “Multifunctional Polymers in Medicine” and the FU Focus Area “Nanoscale”, the collaborative research centers SFB 765 and SFB 1112 (A02, C03) of the German Science Foundation (DFG) and the DFG Priority Program 1313 Biological Responses to Nanoscale Particles.

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None.

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Authors and Affiliations

  1. Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany

    Cornelia Holzhausen, Lars Mundhenk & Achim D. Gruber

  2. Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany

    Dominic Gröger & Rainer Haag

  3. Department of Neuroradiopharmaceuticals, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig, Germany

    Cornelius K. Donat

  4. Institute of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Jörg Schnorr

Authors
  1. Cornelia Holzhausen
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  2. Dominic Gröger
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  3. Lars Mundhenk
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  4. Cornelius K. Donat
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  5. Jörg Schnorr
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  6. Rainer Haag
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  7. Achim D. Gruber
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Corresponding author

Correspondence to Achim D. Gruber.

Additional information

Cornelia Holzhausen: this article is part of the Ph.D thesis of CH.

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Holzhausen, C., Gröger, D., Mundhenk, L. et al. Biodistribution, cellular localization, and in vivo tolerability of 35S-labeled antiinflammatory dendritic polyglycerol sulfate amine. J Nanopart Res 17, 116 (2015). https://doi.org/10.1007/s11051-015-2927-3

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  • DOI: https://doi.org/10.1007/s11051-015-2927-3

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