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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. Toxicity of Dendrimers.

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Toxicity of Dendrimers

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  1. 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. Toxicity of Dendrimers

  2. 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.jpg

  3. 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?

  4. The methods • 4 specific dendrimers • Zebrafish • Collected data • Removal of chorion Concentrations of dendrimers www.nature.com/.../v3/n7/fig_tab/nrc1126_F4.html

  5. What data? • At different concentrations • Over time • Morphological defects

  6. 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

  7. 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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