In vivo proinflammatory activity of generations 0-3 (G0-G3) polyamidoamine (PAMAM) nanoparticles.

Abstract

The aim of this study was to determine whether different generations (G) polyamidoamine (PAMAM) dendrimers possess proinflammatory activities in vivo. Several hundred female CD-1 mice were used to test four different PAMAM dendrimers using the murine air pouch model. Mice received appropriate negative and positive controls or G0-G3 PAMAM nanoparticles at 100 and 500µg/ml into air pouches. Exudates were harvested after 3, 6, 24 and 48h. Cell pellets and supernatants were used to determine the number of total leukocytes and neutrophils and to detect the production of several analytes by an antibody array approach, respectively. One-way analysis of variance was used for statistical analysis. PAMAM dendrimers rapidly increased a leukocyte influx after 3h, the vast majority of cells being neutrophils. This was also observed after 6 and 24h, and resolution of inflammation was noted after 48h. In general, the increased production of a greater number of analytes detected in the exudates after 6h correlated with the number of dendrimer generations (G3>G2>G1>G0). PAMAM dendrimers devoid of any delivering molecules possess proinflammatory activities in vivo by themselves, probably via the production of different chemokines released by air pouch lining cells.