PRECLINICAL STUDIES OF COPPER NANOPARTICLES

Authors

  • Y. S. Stravskyy I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • L. Ya. Fedoniuk I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • O. M. Yarema I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • L. S. Reznichenko F. OVCHARENKO INSTITUTE OF BIOKOLLOID CHEMISTRY, NAS OF UKRAINE, KYIV

DOI:

https://doi.org/10.11603/mcch.2410-681X.2020.v.i3.11546

Keywords:

Cuprum nanoparticles, preclinical study, biosafety, toxicity, antimicrobial action, fungicidal action

Abstract

Introduction. Preclinical study of drugs is an integral part of the drug creation process. Established for the results of preclinical studies, the characteristics of specific pharmacological activity and harmfulness during use and its possible long-term consequences are the main factors that determine the possibility of transferring the drug to commercial release and the feasibility of its medical use.

The aim of the study – to learn the biosafety, acute toxicity, antimicrobial and fungicidal effects of copper nanoparticles.

Research Methods. The biosafety of the synthesized substance of nanoparticles in in vitro tests was determined using cytotoxicity, mutagenicity, molecular genetic (genotoxicity), physiological ("state of the microflora of the human gastrointestinal tract") and biochemical (ATP-ase and lactate activity). Antimicrobial and fungicidal properties of drug were also studied in clinical isolates of infectious and inflammatory pathogens: bacteria S. aureus, E. coli, Proteus mirabilis, K. pneumoniae, Enterobacter aerogenes, P. aeruginosa, fungi of the genus Candida – C. albicans, Candida non-albicans and other micromycetes – Penicillium spp., Paecilomyces lilacinus, A. niger and A. flavus.

Results and Discussion. The interaction of copper nanoparticles with test eukaryotic cells did not lead to the appearance of primary DNA damage, compared with the effect of N-nitrosomethylurea, which is a known genotoxicant. In the samples of test eukaryotic cells of the line treated with copper nanoparticles in a wide concentration range, no cytotoxic effect of the studied nanomaterial was recorded. The experimental substance of copper nanoparticles (CuNP) has a pronounced antimicrobial and fungicidal activity against all studied pathogenic test cultures: both in the initial concentration (32.0 mg/ml for metal) and for its tenfold dilution (3.2 mg/ml in conversion to metal). Complete inhibition of the growth of pathogenic test strains was observed at final inoculation doses of microorganisms on plates from 103 to 105 CFU/cm3. The studied substance of copper nanoparticles also showed antimicrobial and fungicidal action against clinical isolates of pathogens of infectious and inflammatory processes of different localization, namely bacteria and fungi.

Conclusion. Evaluation of acute toxicity of copper nanoparticle substances after a single intravenous injection of white rats depending on the dose level in the range of 14 days of observation allows to cancel the substance of copper nanoparticles up to class IV toxicity (low toxicity).

References

Kotsiubasa, I.Ya. (Ed.). (2006). Doklinichni dosli­dzhennia veterynarnykh likarskykh zasobiv [Preclinical studies of veterinary drugs]. Lviv [in Ukrainian].

Ingle, A.P., Duran, N., & Rai, M. (2014). Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles: a review. Appl. Microbiol. Biotechnol., 98 (3), 1001-1009.

Stefanov, O.V. (Ed.). (2001). Doklinichni dosli­dzhennia likarskykh zasobiv: metod. rekom. [Preclinical studies of medicines: guidelines]. Kyiv [in Ukrainian].

(2009). Pro zatverdzennia Poriadku provedennia doklinichnoho vyvchennia likarskykh zasobiv ta ekspertyzy materialiv doklinichnoho vyvchennia zasobiv: nakaz MOZ Ukrainy № 944 vid 14.12.2009 r. [On the statement of the Order of carrying out preclinical studying of drugs and examination of materials of preclinical studying of medicines: the order of the Ministry of Health of Ukraine No. 944 of December 14, 2009]. Retrieved from: http://zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=z0053–10/ [in Ukrainian].

Viktorov, A.P., Maltsev, V.I., & Belousov, Yu.B. (Eds.). (2007). Bezopasnost lekarstv. Rukovodstvo po farmaknadzoru [Drug safety. Pharmacovigilance guidelines]. Kyiv: Morion [in Ukrainian].

Chekman, I.S., Ulberh, Z.R., Malanchuk, V.O., Horchakova, N.O., & Zupanets, I.A. (2012). Nanonauka, nanobiolohiia, nanofarmatsiia [Nanoscience, nanobiology, nanopharmacy]. Kyiv: Polihraf plius [in Ukrainian].

Trakhtenberh, I.M., Ulberh, Z.R., & Chekman, I.S. (2013). Otsinka bezpeky likarskykh nanopreparativ: metod. rek. [Safety assessment of drug nanopreparations: guidelines]. Kyiv: Ministry of Health of Ukraine [in Ukrainian].

Liao, M., & Liu, H. (2012). Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration. Environ. Toxicol. Pharmacol., 34 (1), 67-80.

Privalova, L.I., Katsnelson, B.A., Loginova, N.V., Gurvich, V.B., Shur, V.Y., Valamina, I.E., & Makeyev, O.H. (2014). Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors. Int. J. Mol. Sci., 15 (7), 12379-12406.

Pelgrift, R.Y., & Friedman, A.J. (2013). Nanotechnology as a therapeutic tool to combat microbial resistance. Adv. Drug Deliv. Rev., 65 (13-14), 1803-1815.

Ghasemian, E., Naghoni, A., Tabaraie, B., & Tabaraie, T. (2012). In vitro susceptibility of filamentous fungi to copper nanoparticles assessed by rapid XTT colorimetry and agar dilution method. J. Mycol. Med., 22 (4), 322-328.

Ren, G., Hu, D., Cheng, E.W.C., Vargas-Reus, M.A., Reip P., & Allaker, R.P. (2009). Characterization of copper oxide nanoparticles for antimicrobial applications. Int. J. Antimicrob. Agents., 33, 587-590.

Holovenko M.Ya. (2007). Nanomedytsyna: dosiahnennia i perspektyvy rozvutku noviynikh tekhnolohii u diahnostytsi i likuvanni [Nanomedicine: achievements and prospects for the development of new technologies in diagnosis and treatment]. Zhurn. AMN Ukrainy – Journal of AMS of Ukraine, 13 (4), 1-23 [in Ukrainian].

Rieznichenko, L.S., Rudenko, A.V., Simnov, P.V., Hruzina, T.H., Ulberh, Z.R., & Chekman, I.S. (2012). Efektyvnist dii nanochastynok midi do zbudnykiv infektsiino-zapalnykh protsesiv riznoi lokalizatsii [The effectiveness of copper nanoparticles to pathogens of infectious and inflammatory processes of different localization]. Visn. Farmatsii – Bulletin of Pharmacy, 3 (71), 75-78 [in Ykrainian].

Published

2020-12-03

How to Cite

Stravskyy, Y. S., Fedoniuk, L. Y., Yarema, O. M., & Reznichenko, L. S. (2020). PRECLINICAL STUDIES OF COPPER NANOPARTICLES. Medical and Clinical Chemistry, (3), 99–106. https://doi.org/10.11603/mcch.2410-681X.2020.v.i3.11546

Issue

Section

ORIGINAL INVESTIGATIONS