Dendrimers toxicity

Duncan and Izzo" listed in their seminal review on dendrimer toxicity some general consideration for polymers and dendrimers for in vivo applications "As a general rule, for any polymeric carrier to be suitable for parenteral application it is essential that the carrier is non-toxic and non-immunogenic, and it should preferably be biodegradable. It must display an inherent body distribution that will allow appropriate tissue targeting to the desired site, but... 

Dendrimer toxicity assessment. Adapted from Duncan, R. Izzo, L. Adv. Dmg Deliv. Rev. 2005,57,2215. ... 

Toxicity analysis of nanosized constructs is critical for any of them to be useful clinically and have the potential to be greatly informed by pharmacokinetic studies. Toxicity of dendrimers have been reviewed recently and it was found that one mechanism of dendrimer toxicity is surface charge amine terminated dendrimers were detrimental to cells, while neutral and negative surface charges were much less toxic, or had no toxicity at all. 

In macromolecular dmg delivery systems, dmgs are attached to polymeric compounds, such as synthetic polymers [60], dendrimers [61], and antibodies [62], in order to enhance the delivery of the active substance to the diseased tissue and to reduce the toxicity to healthy tissue. The use of macromolecular delivery systems provides several advantages extension of the half-life of the dmg, the ability to introduce targeting moieties into the carrier, the possibility of triggered dmg release, and the aforementioned reduced cytotoxicity. 

Lesniak W, Bielinska AU, Sun K, Janczak KW, Shi X, Baker JR, Balogh LP (2005) Silver/ dendrimer nanocomposites as biomarkers fabrication, characterization, in vitro toxicity, and intracellular detection. Nano Lett 5 2123-2130... 

As mentioned in the previous section, there are good reasons to search for new reaction conditions for Heck and related reactions, which permit catalyst recovery, the use of less toxic solvents, and simpler product recovery. The use of liquid or supercritical (SC) CO2 addresses all of these issues [171]. Until recently, however, the use of supercritical COj had been limited to organometallic Pd complexes functionalized with perfluorinated ligands [172-174], due to the limited solubility of metal colloids in CO2, and often required the use of water as a co-solvent [175]. The work described here shows that dendrimers can be used to solubilize Pd nanoclusters in liquid and SC CO2. This new finding opens the door to the combined benefits of a catalyst that promotes Heck couplings, but without the need for toxic ligands or solvents. 

Duncan R, Izzo L. Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 2005 57 2215-2237. 

Bradley developed a solid-phase synthesis of peptidomimetic dendrimers using the lysine-like peptoid monomer 25 [226] which led to G1-G3 dendrimers, bearing both primary and secondary amino groups on the periphery, with promising transfection abilities and no toxicity [227] (see Fig. 25). 

Kim TI, Baek JU, Zhe BC et al (2007) Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier. Biomaterials 28 2061-2067... 

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