Journal of Clinical Toxicology
Open Access

In vitro and in vivo inflammatory effects of PAMAM dendrimers nanoparticles

3^rd International Summit on Toxicology & Applied Pharmacology

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore, USA

Isabelle Durocher, Claudie Noël and Denis Girard

Posters: J Clin Toxicol

Abstract :

S everal types of dendrimer nanoparticles (NPs) have been developed for various biomedical applications, including imaging agents and drug delivery systems. The polyamidoamine dendrimers (PAMAM) are among the most widely used and, despite their multiple functions, very few nanotoxicological studies have been performed. Since inflammation is one of the most toxic effects of NPs reported in the literature, we evaluated the impact of four generations (G) of PAMAM NPs (G0, G1, G2 and G3) on neutrophils, key player cells in inflammation. Because of the importance of neutrophil apoptosis in the resolution of inflammation, we determined if their basal apoptotic rate could be altered by the NPs. Also, we evaluated if the NPs could attract neutrophils in vivo . To do so, freshly isolated human neutrophils were incubated with various concentrations of NPs and the apoptotic rate was determined after 24 h by cytology and by fluorescence microscopy. For in vivo cell infiltration, we used the murine air pouch model in which 100 or 500 μg/ml of the NPs were administered into the pouch for 6 or 24 h. Exudates were harvested for cell counting and a fraction was used to perform western blot and zymography experiments to determine gelatinase activity. All the NPs (G0 to G3) were found to increase the apoptotic rate at a concentration greater than 100 μg/ml. Although only G1-500, G2-500 and G3-100 and 500 μg/ml were found to significantly increase the total number of leukocytes recruited in vivo , an increase number of neutrophils was consistently observed in all tested conditions. Results of the zymography experiments suggest a correlation between the number of neutrophils and the gelatinase activity. Unexpectedly, our results indicate that the NPs are proapoptotic in vitro (anti-inflammatory), but induce a neutrophilic infiltration (pro- inflammatory) in vivo