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Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice

Liu, Tianlong, Li, Linlin, Teng, Xu, Huang, Xinglu, Liu, Huiyu, Chen, Dong, Ren, Jun, He, Junqi, Tang, Fangqiong
Biomaterials 2011 v.32 no.6 pp. 1657-1668
biocompatibility, death, drug delivery systems, hepatocytes, intravenous injection, lethal dose 50, mice, nanoparticles, phagocytes, silica, spleen, toxicity testing, transmission electron microscopy
Mesoporous hollow silica nanoparticles (MHSNs) are emerging as one of the new and promising nanomaterials for biomedical applications, but the biocompatibility of MHSNs in vivo has received little attention. In the present study, the systematic single and repeated dose toxicity, biodistribution and clearance of MHSNs in vivo were demonstrated after intravenous injection in mice. For single dose toxicity, lethal dose 50 (LD₅₀) of 110 nm MHSNs was higher than 1000 mg/kg. Further repeated dose toxicity studies indicated no death was observed when mice were exposed to MHSNs at 20, 40 and 80 mg/kg by continuous intravenous administration for 14 days. These results suggest low toxicity of MHSNs when intravenous injection at single dose or repeated administrations. ICP–OES and TEM results show that the MHSNs mainly accumulate in mononuclear phagocytic cells in liver and spleen. In addition, these particles could be excreted from the body and the entire clearance time of the particles should be over 4 weeks. These findings would be useful for future development of nanotechnology-based drug delivery system and other biomedical applications.