Toxicity of Dendrimers

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Toxicity of Dendrimers

• Anne Franzene
• June 15, 2008
• BBSI presentation
• King Heiden, T.C., Dengler, E., Kao, W.J.,
  Heideman, W., and Peterson, R.E. Developmental
  toxicity of low generation PAMAM dendrimers in
  zebrafish. Toxicology and Applied Pharmacology.
  225 (2007) 70-79.

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Some background information

• Dendrimers
• Previous studies of toxicity
• RGD (Arg-Gly-Asp) peptide
• Zebrafish

www.umich.edu/bhgroup/dendrimer/dendrimers.html
http//www.sanger.ac.uk/Info/Press/gfx/zebrafish.j
pg
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The question

• What is the toxicity of low generation PAMAM
  dendrimers?
• More specifically
• What is the developmental toxicity of G3.5 and
  G4.0 dendrimers in zebrafish?
• What is the developmental toxicity of
  RGD-conjugated G3.5 and G4.0 dendrimers in
  zebrafish?

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The methods

• 4 specific dendrimers
• Zebrafish
• Collected data
• Removal of chorion

Concentrations of dendrimers
www.nature.com/.../v3/n7/fig_tab/nrc1126_F4.html
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What data?

• At different concentrations
• Over time
• Morphological defects

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The results

• G3.5 PAMAM dendrimers
• No increase in mortality
• No increase in sublethal signs of toxicity or
  malformations
• G4.0 PAMAM dendrimers
• Time and concentration dependence
• RGD-conjugated dendrimers
• Showed less toxicity

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The conclusions

• Confirmed that zebrafish is a good system for
  assessing toxicity
• RGD-G3.5 dendrimers show promise as vectors for
  targeted drug delivery

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