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3H Dendrimer Nanoparticle Organ/Tumor Distribution

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Abstract

Purpose. To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.

Methods. Neutral (NSD) and positive surface charged (PSD) generation 5 (d =5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples. Mice were also monitored for acute toxicity.

Results. Both PSD and NSD localized to major organs and tumor. Dendrimers cleared rapidly from blood, with deposition peaking at 1 h for most organs and stabilizing from 24 h to 7 days postinjection. Maximal excretion occurred via urine within 24 h postinjection. Neither dendrimer showed acute toxicity.

Conclusions. Changes in the net surface charge of polycationic PAMAMs modify their biodistribution. PSD deposition into tissues is higher than NSD, although the biodistribution trend is similar. Highest levels were found in lungs, liver, and kidney, followed by those in tumor, heart, pancreas, and spleen, while lowest levels were found in brain. These nanoparticles could have future utility as systemic biomedical delivery devices.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109

    Shraddha S. Nigavekar, Lok Yun Sung, Mikel Llanes, Areej El-Jawahri, Theodore S. Lawrence & Mohamed K. Khan

  2. Michigan Memorial Phoenix Project, University of Michigan, Ann Arbor, MI, 48109

    Christopher W. Becker

  3. Department of Internal Medicine, Center for Biologic Nanotechnology, University of Michigan, Ann Arbor, MI, 48109

    Lajos Balogh

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  1. Shraddha S. Nigavekar
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  2. Lok Yun Sung
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  7. Lajos Balogh
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  8. Mohamed K. Khan
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Nigavekar, S.S., Sung, L.Y., Llanes, M. et al. 3H Dendrimer Nanoparticle Organ/Tumor Distribution. Pharm Res 21, 476–483 (2004). https://doi.org/10.1023/B:PHAM.0000019302.26097.cc

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