Pre-clinical and behavioural toxicity profile of PAMAM dendrimers in mice

Abstract

A toxicity study of different polyamidoamine (PAMAM) dendrimers in Swiss albino mice was performed with a clinical overview. In the current study, mice were treated with various G4 dendrimers (NH2 and OH surface groups) at different dosage levels (low, medium and high) via the intraperitoneal route for 15 consecutive days, followed by a 15 day recovery period. The toxicity profile was investigated in mice for their general behaviour, feed intake, body weight, carbohydrate, lipid and protein metabolism, haematological parameters, histopathology and cell viability. No significant differences were observed in feed intake, body weight and organ weight among the various dendrimer-fed groups and control. In general, dendrimers have no significant effect on the carbohydrate and lipid metabolism. However, declined glucose levels in the high-NH2 dose group indicates the interference of this dosage level with glucose metabolism. Although all the test groups showed activity in the normal range, the high-NH2 group showed comparatively higher alanine aminotransferase and aspartate aminotransferase activity. Minor, but insignificant (p <0.05), differences were observed in the red blood cells, haematocrit value and haemoglobin of the treated group when compared to the control group in a dose-dependent manner, but these recovered during the recovery period. There was no effect on other haematological parameters. Histopathological evaluation of dendrimer-treated groups did not reveal any abnormalities in the low- and medium-dose groups, but at a high dose level, toxicity was observed in the liver and kidney. However, after the recovery period, toxicity in the high dose level was not found. A cell viability study of cationic dendrimers has shown reduced cytotoxicity after the complexation with a guest molecule such as indomethacin. This study showed that dendrimers are not toxic, in general. The high dose of G4-NH2 displayed some toxicity; however, that too was recovered after some time. This journal is © 2009 The Royal Society.