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Pharmaceutical Research

, Volume 21, Issue 3, pp 476–483 | Cite as

3H Dendrimer Nanoparticle Organ/Tumor Distribution

  • Shraddha S. Nigavekar
  • Lok Yun Sung
  • Mikel Llanes
  • Areej El-Jawahri
  • Theodore S. Lawrence
  • Christopher W. Becker
  • Lajos Balogh
  • Mohamed K. Khan
Article

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.

biodistribution melanoma PAMAM dendrimers prostate cancer tritiated nanoparticles 

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Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • Shraddha S. Nigavekar
    • 1
  • Lok Yun Sung
    • 1
  • Mikel Llanes
    • 1
  • Areej El-Jawahri
    • 1
  • Theodore S. Lawrence
    • 1
  • Christopher W. Becker
    • 2
  • Lajos Balogh
    • 3
  • Mohamed K. Khan
    • 1
  1. 1.Department of Radiation OncologyUniversity of MichiganAnn Arbor
  2. 2.Michigan Memorial Phoenix ProjectUniversity of MichiganAnn Arbor
  3. 3.Department of Internal Medicine, Center for Biologic NanotechnologyUniversity of MichiganAnn Arbor

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