An influence of the cream with cerium dioxide nanoparticles on some vital signs of rats in the setting of a topical application in a chronic experiment

Keywords: cerium dioxide nanoparticles, chronic toxicity, preclinical studies, topical application, Wistar rats


Melanoma and non-melanoma cancers are global healthcare problems nowadays. Ultraviolet (UV) radiation exposure is one of the risk factors of development of these pathologies. An introduction of sunscreen creams with cerium dioxide nanoparticles (CDN) in medical practice will widen the spectrum of measures of prevention of UV-induced injuries, namely, skin malignancies. Development of such products includes the complex of non-clinical studies in the field of safety pharmacology.

The study on an influence of the cream with CDN on some vital signs of rats in the setting of a topical application in a chronic experiment.

Standardized CDN 6–15 nm in size were synthesized in TOV ‘NanoMedTech’, the dermal cream with 0.25% CDN was developed in SSI ‘Institute for Single Crystals’ of NAS of Ukraine. The experiment was carried out on 100 white female Wistar rats. Animals were allocated into 5 groups with 20 rats each: an intact control, an application of the cream with CDN in the doses of 0.1, 0.5, and 1.0 g/kg, an application of a cream base (placebo). The cream with CDN was applied on skin once a day during 6 months. Toxicity was evaluated on the basis of following indices: survivability, overall health and behavior of animals, ingestion of food and water, body mass dynamics, hematological and serum biochemical indices, macroscopic structure and mass coefficients of internal organs.

No mortality, deterioration of overall health, changes in behavior and ingestion of food and water were observed in groups of an application of the cream with CDN; body mass dynamics were positive. There were no critical differences in hematological (hemoglobin; erythrocyte, thrombocyte, leukocyte count; leucogram) and serum biochemical (alanine aminotransferase, aspartate aminotransferase, total protein, albumin, creatinine, glucose, cholesterol, potassium, sodium, phosphorus, chlorides) indices between groups of an application of the cream with CDN and control groups over a period of the experiment. A macroscopic evaluation of condition of internal organs didn’t show any toxic effect of the cream with CDN, and mass coefficients were standard for rats and basically didn’t differ from those in control groups.

The cream with CDN in the doses of 0.1, 0.5, and 1.0 g/kg in the setting of a topical application in rats once a day during 6 months is safe – it doesn’t cause animal mortality, doesn’t influence overall health, behavior of animals, ingestion of food and water, doesn’t contribute to negative body mass dynamics, doesn’t have a negative impact on hematological and serum biochemical indices, and doesn’t alter a macroscopic structure and mass coefficients of internal organs of rats.


1. Apalla Z., Nashan D., Weller R. B. et al. Skin cancer: epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches // Dermatol. Ther. (Heidelb). – 2017. – V. 7, Suppl. 1. – P. 5–19.
2. Kolesnik O. O., Fedorenko Z. P., Mykhailovych Yu. Y. et al. Biuleten Natsionalnoho kantser-reiestru № 19 – «Rak v Ukraini, 2016–2017». – Kyiv: Natsionalnyi instytut raku, 2018.
3. Martens M. C., Seebode C., Lehmann J. et al. Photocarcinogenesis and skin cancer prevention strategies: an update // Anticancer Res. – 2018. – V. 38, N 2. – P. 1153–1158.
4. Stiefel C., Schwack W. Photoprotection in changing times – UV filter efficacy and safety, sensitization processes and regulatory aspects // Int. J. Cosmet. Sci. – 2015. – V. 37, N 1. – P. 2–30.
5. Particulate products: tailoring properties for optimal performance / Ed. H. G. Merkus, G. M. H. Meesters. – Springer International Publishing Switzerland, 2014. – 469 p.
6. Shcherbakov A. B., Ivanova O. S., Spivak N. Ya., Kozyk V. V., Ivanov V. K. Sintez i biomeditsinskie primeneniia nanodispersnogo dioksida tseriia. – Tomsk: Izdatelskii dom Tomskogo gosudarstvennogo universiteta, 2016.
7. Caputo F., De Nicola M., Sienkiewicz A. et al. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis // Nanoscale. – 2015. – V. 7, N 38. – P. 15643–15656.
8. Li Y., Li P., Yu H. et al. Recent advances (2010–2015) in studies of cerium oxide nanoparticles’ health effects // Environ. Toxicol. Pharmacol. – 2016. – V. 44. – P. 25–29.
9. Chen B. H., Stephen Inbaraj B. Various physicochemical and surface properties controlling the bioactivity of cerium oxide nanoparticles // Crit. Rev. Biotechnol. – 2018. – V. 38, N 7. – P. 1003–1024.
10. Yefanov V. S., Zaychenko G. V., Nikitina N. S., Pokotylo O. A. Doslidzhennia hostroi toksychnosti kremu z nanochastynkamy dioksydu tseriiu / V natsionalnyi ziizd farmakolohiv Ukrainy. – Zaporizhzhia: Vydavnytstvo ZDMU, 2017. ‒ p. 43.
11. Pokotylo O. A., Nikitina N. S. The study of subchronic toxicity of the cream with cerium dioxide nanoparticles / Topical Issues of New Drugs Development: abstracts of XXV International Scientific and Practical Conference of Young Scientists and Students, Kharkiv, 18–20. 04. 2018. – Kharkiv: Vydavnytstvo NFAU, 2018. – S. 335–336.
12. Stefanov O. V. (Ed.). Doklinichni doslidzhennia likarskykh zasobiv: metodychni rekomendatsii. – Kyiv: Avitsena, 2001. – 528 s.
13. Henry’s clinical diagnosis and management by laboratory methods / Ed. R. A. McPherson, M. R. Pincus. – 22-nd ed. – Philadelphia: Elsevier/Saunders, 2011. – 1568 p.
14. Sunheimer R. L., Graves L. Clinical laboratory chemistry. – Upper Saddle River: Pearson, 2011. – 688 p.
15. IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.
16. Marino D. J. Age-specific absolute and relative organ weight distributions for Fischer 344 rats // J. Toxicol. Environ. Health A. – 2012. – V. 75, N 24. – P. 1484–1516.
17. Charbgoo F., Ahmad M. B., Darroudi M. Cerium oxide nanoparticles: green synthesis and biological applications // Int. J. Nanomedicine. – 2017. – V. 12. – P. 1401–1413.
18. Gagnon J., Fromm K. M. Toxicity and protective effects of cerium oxide nanoparticles (nanoceria) depending on their preparation method, particle size, cell type, and exposure route // Eur. J. Inorg. Chem. – 2015. – N 27. – P. 4510–4517.
19. Rzigalinski B. A., Carfagna C. S., Ehrich M. Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety // Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. – 2017. – V. 9, N 4. – P. 1–17.
20. Yokel R. A., Hussain S., Garantziotis S. et al. The Yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity // Environ. Sci. Nano. – 2014. – V. 1, N 5. – P. 406–428.
21. Rajeshkumar S., Naik P. Synthesis and biomedical applications of cerium oxide nanoparticles – a review // Biotechnol. Rep. (Amst). – 2017. – V. 17. – P. 1–5.
22. Herrling T., Seifert M., Jung K. Cerium dioxide: future UV-filter in sunscreen? // SOFW J. – 2013. – V. 139, N 5. – P. 10–14.
23. McSweeney P. C. The safety of nanoparticles in sunscreens: an update for general practice // Aust. Fam. Physician. – 2016. – V. 45, N 6. – P. 397–399.
24. Gulson B., McCall M. J., Bowman D. M. et al. A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies // Arch. Toxicol. – 2015. – V. 89, N 11. – P. 1909–1930.
25. Larese Filon F., Mauro M., Adami G. et al. Nanoparticles skin absorption: new aspects for a safety profile evaluation // Regul. Toxicol. Pharmacol. – 2015. – V. 72, N 2. – P. 310–322.
How to Cite
Zaychenko, G. V., Pokotylo, O. A., & Nikitina, N. S. (2019). An influence of the cream with cerium dioxide nanoparticles on some vital signs of rats in the setting of a topical application in a chronic experiment. Farmatsevtychnyi Zhurnal, (2), 88-98.