Pharmaceutical Research

, Volume 21, Issue 3, pp 476–483

3H Dendrimer Nanoparticle Organ/Tumor Distribution

Authors

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

DOI: 10.1023/B:PHAM.0000019302.26097.cc

Cite this article as:
Nigavekar, S.S., Sung, L.Y., Llanes, M. et al. Pharm Res (2004) 21: 476. doi:10.1023/B:PHAM.0000019302.26097.cc

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.

biodistributionmelanomaPAMAM dendrimersprostate cancertritiated nanoparticles

Copyright information

© Plenum Publishing Corporation 2004