Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish. Public

http://ir.library.oregonstate.edu/concern/honors_college_theses/2801pj34b

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  • Dendrimers are well-defined, polymeric nanomaterials currently being investigated for their biomedical applications. Initially, higher generation (size) dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM) dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers.
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