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.
Nanoparticle Radiolabeling Liquid scintillation counting Radioluminography Nanotoxicology Health effects
Dendritic polyglycerol sulfate
Hematoxylin and eosin
Light microscopic autoradiography
Liquid scintillation counting
Mononuclear phagocyte system
Photostimulable phosphor plate
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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
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