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Related Experiment Videos

3H dendrimer nanoparticle organ/tumor distribution.

Shraddha S Nigavekar1, Lok Yun Sung, Mikel Llanes

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

Pharmaceutical Research
|April 9, 2004
PubMed
Summary

Surface charge affects poly(amidoamine) (PAMAM) dendrimer biodistribution in cancer models. Positively charged dendrimers showed higher tissue deposition than neutral ones, with rapid clearance and no acute toxicity observed.

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Area of Science:

  • Nanotechnology
  • Biomedical Engineering
  • Pharmacology

Background:

  • Poly(amidoamine) (PAMAM) dendrimers are versatile nanoparticles with potential biomedical applications.
  • Their surface charge is a critical factor influencing their behavior in biological systems.
  • Understanding in vivo biodistribution is essential for developing effective drug delivery systems.

Purpose of the Study:

  • To investigate the in vivo biodistribution of differently charged PAMAM dendrimers.
  • To compare the biodistribution of neutral (NSD) and positively charged (PSD) generation 5 PAMAM dendrimers.
  • To evaluate PAMAM dendrimer distribution in B16 melanoma and DU145 prostate cancer mouse models.

Main Methods:

  • Synthesis of 3H-labeled neutral (NSD) and positively charged (PSD) generation 5 PAMAM dendrimers.

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  • Intravenous injection of dendrimer derivatives into tumor-bearing mice.
  • Biodistribution assessment using liquid scintillation counting of tritium in tissues and excreta.
  • Monitoring of mice for acute toxicity.

    • Main Results:

    • Both PSD and NSD PAMAM dendrimers localized to major organs and tumors.
    • Rapid blood clearance was observed, with peak deposition in organs at 1 hour post-injection.
    • Maximal excretion occurred via urine within 24 hours, and no acute toxicity was detected.
    • PSD dendrimers exhibited higher tissue deposition compared to NSD dendrimers.

    Conclusions:

    • Surface charge significantly modifies PAMAM dendrimer biodistribution in vivo.
    • The biodistribution trend was similar for both PSD and NSD, with highest levels in lungs, liver, and kidney.
    • PAMAM dendrimers show promise as systemic biomedical delivery devices due to their biodistribution profile and safety.