DOI: https://doi.org/10.22263/2312-4156.2019.1.59
Zaychenko G.V., Pokotylo O.A.
Experimental study of pharmacokinetic profile of the cream with cerium dioxide nanoparticles
Bogomolets National Medical University, Kiev, Ukraine
Vestnik VGMU. 2019;18(1):59-64.
Abstract.
Objectives. To study some parameters of pharmacokinetics of the cream with cerium dioxide nanoparticles (CDN) on single skin application in rats.
Material and methods. CDN were synthesized in LLC «NanoMedTech», the dermal cream with 0,25% CDN was developed in NTC «Institute for Monocrystals» of NAS of Ukraine. The cream with CDN was applied in rats epicutaneously in the dose of 2 mg/cm2 according to the groups: 1) intact control; 2–6) application of the cream with subsequent euthanasia after 2, 6, 12, 24, and 48 hours; 7–11) application of the cream with sudsequent ultraviolet (UV) exposure and euthanasia after 2, 6, 12, 24, and 48 hours. Blood and application site skin samples, as well as the liver, kidneys, and the spleen, were taken after euthanasia. The cerium concentration was measured by means of inductively coupled plasma atomic emission spectroscopy method.
Results. No cerium was detected in the blood and internal organs of rats, even after UV exposure. An accumulation of CDN in the skin without concentration changes was observed during 24 hours. There were no changes of the studied parameter value in 24 hours on comparing groups with or without UV exposure, which indicates an absence of UV effect on absorption of CDN.
Conclusions. On single skin application of the cream with CDN in the dose of 2 mg/cm2 in rats, cerium is accumulated in the skin during 24 hours with further decrease in concentration, it isn’t found in the blood and internal organs, which suggests the presence of a long-term photoprotective effect of CDN without resorptive action.
Key words: cerium dioxide nanoparticles, pharmacokinetics, skin application, photodynamic injury, rats.
Referenses
1. Nashan D, Weller RB, Castellsagué X. Skin cancer: epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther (Heidelb). 2017 Jan;7(Suppl 1):5-19. doi: http://dx.doi.org/10.1007/s13555-016-0165-y
2. Martens MC, Seebode C, Lehmann J, Emmert S. Photocarcinogenesis and skin cancer prevention strategies: an update. Anticancer Res. 2018 Feb;38(2):1153-1158. doi: http://dx.doi.org/10.21873/anticanres.12334
3. Didona D, Paolino G, Bottoni U, Cantisani C. Non melanoma skin cancer pathogenesis overview. Biomedicines. 2018 Jan;6(1). pii: E6. doi: http://dx.doi.org/10.3390/biomedicines6010006
4. Dunaway S, Odin R, Zhou L, Ji L, Zhang Y, Kadekaro AL. Natural antioxidants: multiple mechanisms to protect skin from solar radiation. Front Pharmacol. 2018 Apr;9:392. doi: http://dx.doi.org/10.3389/fphar.2018.00392
5. Stiefel C, Schwack W. Photoprotection in changing times – UV filter efficacy and safety, sensitization processes and regulatory aspect. Int J Cosmet Sci. 2015 Feb;37(1):2-30. doi: http://dx.doi.org/10.1111/ics.12165
6. Merkus HG, Meesters GMH, ed. Particulate products: tailoring properties for optimal performance. Switzerland: Springer International Publishing; 2014. 469 p.
7. Shcherbakov AB, Ivanova OS, Spivak NYa, Kozik VV, Ivanov VK. Synthesis and biomedical applications of nanodisperse cerium dioxide. Tomsk, RF: ID TGU; 2016. 476 р. (In Russ.)
8. Caputo F, De Nicola M, Sienkiewicz A, Giovanetti A, Bejarano I, Licoccia S, et al. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis. Nanoscale. 2015 Oct;7(38):15643-56. doi: http://dx.doi.org/10.1039/c5nr03767k
9. Li Y, Li P, Yu H, Bian Y. Recent advances (2010–2015) in studies of cerium oxide nanoparticles’ health effects. Environ Toxicol Pharmacol. 2016 Jun;44:25-9. doi: http://dx.doi.org/10.1016/j.etap.2016.04.004
10. Efanov VS, Zaychenko GV, Nikitina NS, Pokotilo OA. Study of acute toxicity of the cream with nanoparticles of cerium dioxide. V: Tezi dopovіdei V natsіonal’nogo z’їzdu farmakologіv Ukraїni, m Zaporіzhzhia, 18–20 zhovtnia 2017 r. Zaporizhia, Ukraine; 2017. Р. 43. (In Ukr.)
11. Pokotylo OA, Nikitina NS. The study of subchronic toxicity of the cream with cerium dioxide nanoparticles. В: Topical Issues of New Drugs Development: abstracts of XXV International Scientific and Practical Conference of Young Scientists and Students, m Kharkіv, 18–20 kvіt 2018 r. Kharkiv, Ukraine: Vid-vo NFaU; 2018. Р. 335-6.
12. Stefanov OV, red. Preclinical drug trials: metod rek. Kiїv, Ukraina: Avіtsena; 2001. 528 р. (In Ukr.)
13. Gulson B, McCall MJ, Bowman DM, Pinheiro T. 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 Nov;89(11):1909-30. doi: http://dx.doi.org/10.1007/s00204-015-1564-z
14. Larese Filon F, Mauro M, Adami G, Bovenzi M, Crosera M. Nanoparticles skin absorption: New aspects for a safety profile evaluation. Regul Toxicol Pharmacol. 2015 Jul;72(2):310-22. doi: http://dx.doi.org/10.1016/j.yrtph.2015.05.005
15. Gulson B, Wong H, Korsch M, Gomez L, Casey P, McCall M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012 Mar;420:313-8. doi: http://dx.doi.org/10.1016/j.scitotenv.2011.12.046
Information about authors:
Zaychenko G.V. – Doctor of Medical Sciences, professor, head of the Chair of Pharmacology, Bogomolets National Medical University;
Pokotylo O.A. – postgraduate of the Chair of Pharmacology, Bogomolets National Medical University.
Correspondence address: Ukraine, 03057, Kiev, 34 Pobedy ave., Bogomolets National Medical University, Chair of Pharmacology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Oksana A. Pokotylo.
