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

  • Cornelia Holzhausen
  • Dominic Gröger
  • Lars Mundhenk
  • Cornelius K. Donat
  • Jörg Schnorr
  • Rainer Haag
  • Achim D. GruberEmail author
Research Paper

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.

Keywords

Nanoparticle Radiolabeling Liquid scintillation counting Radioluminography Nanotoxicology Health effects 

Abbreviations

Cmax

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

Notes

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.

Conflicts of interest

None.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Cornelia Holzhausen
    • 1
  • Dominic Gröger
    • 2
  • Lars Mundhenk
    • 1
  • Cornelius K. Donat
    • 3
  • Jörg Schnorr
    • 4
  • Rainer Haag
    • 2
  • Achim D. Gruber
    • 1
    Email author
  1. 1.Institute of Veterinary PathologyFreie Universität BerlinBerlinGermany
  2. 2.Institute of Chemistry and BiochemistryFreie Universität BerlinBerlinGermany
  3. 3.Department of NeuroradiopharmaceuticalsHelmholtz-Zentrum Dresden-RossendorfLeipzigGermany
  4. 4.Institute of RadiologyCharité-Universitätsmedizin BerlinBerlinGermany

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