Toxicity, biodistribution and oxidative damage caused by zirconia nanoparticles after intravenous injection

Background: As a promising nanomaterial for biomedical applications, zirconia nanoparticles (ZrO(2)) have aroused concern recently, but the toxicity of ZrO(2) in vivo has received little attention. Purpose: The aim of this study is to demonstrate the systematic single dose toxicity, biodistribution and oxidative damage of ZrO(2) in vivo after intravenous injection in mice. Materials and methods: Ten ICR mice were used at the high dose of ZrO(2) including 600, 500, 400 and 300mg/kg. Maximum tolerated dose (MTD) of 150 nm ZrO(2) was determined as 500mg/kg. Hematology analysis and blood biochemical assay were determined for the evaluation of oxidative damage caused by ZrO(2). Biodistribution of ZrO(2) was investigated by ICP-OES and TEM. Results: Mice treated with higher dose (500mg/kg) showed significant spread in white blood cell counts (p<0.05). Especially, the serum ALT levels of 500mg/kg groups increased significantly (p<0.05) compared with the control group. ZrO(2) particles would not induce any changes in appearance and micromorphology of liver at 100 and 350mg/kg. Spleen samples showed no significant changes in micromorphology of the lymphoid follicles and in the size of the red pulp after injection of ZrO(2) at all doses. The serum of ZrO(2)-treated animals (350 and 500mg/kg) has reduced levels of SOD compared to the control group (p<0.05). ZrO(2) persists in membrane-enclosed vesicles called lysosomes in the liver and spleen macrophages without abnormal changes of ultrastructure. Conclusion: These findings would contribute to the future development of ZrO(2)-based drug delivery system and other biomedical applications.