Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice

Abstract

Background

The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs) and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G₄@IONPs).

Materials and methods

IONPs were synthesized via co-precipitation and coated with the fourth generation (G₄) of polyamidoamine (PAMAM) dendrimer. To determine the biodistribution, 5 mg/mL G₄@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS) at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G₄@IONPs, different concentrations of G₄@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G₄@IONPs on the liver and kidney tissues.

Results

The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after injection. Toxicity assessments revealed a significant increase in blood urea nitrogen (BUN) and direct bilirubin at the concentration of 10 mg/kg. Also, in this concentration, histopathological abnormalities were detected in liver tissue.

Conclusion

Although more systematic studies are still required, our results encouraged the future investigations of G₄@IONPs in biomedical applications.

Keywords:

• G₄@IONPs
• biodistribution
• pharmacokinetics
• toxicity

Acknowledgments

This research was supported by a grant from Tehran University of Medical Sciences (grant no. 28169).

Disclosure

The authors report no conflicts of interest in this work.