Biocompatibility studies on cerium oxide nanoparticles - combined study for local effects, systemic toxicity and genotoxicity via implantation route

V Kalyanaraman; Sangeetha Vasudevaraj Naveen; N Mohana; R M Balaje; K R Navaneethakrishnan; B Brabu; S S Murugan; T S Kumaravel

doi:10.1039/c8tx00248g

Biocompatibility studies on cerium oxide nanoparticles - combined study for local effects, systemic toxicity and genotoxicity via implantation route

Toxicol Res (Camb). 2018 Oct 18;8(1):25-37. doi: 10.1039/c8tx00248g. eCollection 2019 Jan 1.

Authors

V Kalyanaraman¹, Sangeetha Vasudevaraj Naveen¹, N Mohana¹, R M Balaje¹, K R Navaneethakrishnan¹, B Brabu², S S Murugan^{1

3}, T S Kumaravel^{1

3}

Affiliations

¹ GLR Laboratories Private Limited , 444 Gokulam Street , Mathur , Chennai 600068 , India . Email: kumaravelts@glrlabs.com.
² Nanoregulatory Platform , Pharma Chemistry , Drug Discovery and Development , Instituto Italiano di Tecnologia (IIT) , Genova 16163 , Italy.
³ GLR Laboratories (Europe) Private Limited , No 4 , The Exchange , Colworth Science Park , Sharnbrook MK44 1LZ , UK.

Abstract

An implantation study of cerium oxide nanoparticles (CeO2-NP) combined with 28-day systemic toxicity and genotoxicity studies aligned to current regulatory standards was conducted. The results suggested that local tissue reactions caused by CeO2-NP was minimal (implantation irritation index of less than 3) and was better tolerated than most other implant materials tested in our laboratory. Furthermore, CeO2-NP showed virtually no systemic toxicity or in vivo micronucleus induction in bone marrow via implantation route. Chemical analysis showed that CeO2-NP migrated from the implant sites (250 mg per site) in low levels and was deposited predominantly in liver (191.8 ± 35.1 ng g^-1 of tissue; P < 0.01), lungs (263.4 ± 30.9 ng g^-1 of tissue; P < 0.001), spleen (211.2 ± 6.5 ng g^-1 of tissue; P < 0.001) and kidneys (272.8 ± 20.4 ng g^-1 of tissue; P < 0.001). These observations provide a base line biocompatibility and toxicity data on CeO2-NP. The current findings will also be useful in defining standards for nanoparticle containing biomaterials and devices.