In vivo and in vitro cytotoxicity and mutagenicity considerations of poly (amido amine) dendrimer

Abstract

A lot of chemicals such as poly (amidoamine) (PAMAM-NH2) dendrimers have pharmaceutical applications, but the major problem with PAMAM-NH2 is their cytotoxicity and mutagenicity. In this research, we have investigated the cytotoxicity and mutagenicity of various generations of PAMAM-NH2 (G2.0, G3.0, G4.0, and G5.0). The cytotoxicity of PAMAM-NH2 at the dilutions of 0.01, 0.001 and 0.0001(W/W) to human mesenchymal stem cells (MSCs) and human gastric adenocarcinoma (AGS) cells was determined using the standard methyl-thiazol-tetrazolium (MTT) assay. To determine mean lethal dose (LD50) of PAMAM-NH2 at doses of 30, 47, 73.5, 115 and 180 mg/kg, 125 Bagg albino/c (BALB/c) mice (8–10 weeks of age, weighing approximately 20 g) were used and also, for determining the mutagenicity effect of PAMAM-NH2, 50?L volume of this substance in the Ame’s test with S. typhimurium was applied. In the MTT assay the most toxic effects, on both of the cell lines, were related to the time when G2.0, G3.0, G4.0 and G5.0 were applied at different dilution of 0.01, 0.001, 0.0001(W/W), respectively. LD50 was determined 73.5 mg/kg. Also in the Ame’s test, the number of reverted colonies was increased by applying higher generations and inhibition percentages of PAMAM-NH2 that were 69.47%, 68.42%, 64.210% and 64.21% for G2.0, G3.0, G4.0 and G5.0, respectively. According to these results, PAMAM-NH2 generations had cytotoxicity effects on MSCs and AGS cells; also toxicity and mutagenicity of the substance were proved in mice and S. typhimurium, respectively. So in order to use PAMAM-NH2 in pharmaceuticals, it must be subjected to various tests to ensure its safety. آ© 2015 by Kermanshah University of Medical Sciences.