Antimicrobial Activity of Citrate-Coated Cerium Oxide Nanoparticles

Abstract

The purpose of this study was to investigate the antimicrobial activity of citrate-stabilized sols of cerium oxide nanoparticles at different concentrations via different microbiological methods and to compare the effect with the peroxidase activity of nanoceria for the subsequent development of a regeneration-stimulating medical and/or veterinary wound-healing product providing new types of antimicrobial action. The object of this study was cerium oxide nanoparticles synthesized from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid (the size of the nanoparticles was 3–5 nm, and their aggregates were 60–130 nm). Nanoceria oxide sols with a wide range of concentrations (10−1–10−6 M) as well as powder (the dry substance) were used. Both bacterial and fungal strains (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Candida albicans, Aspergillus brasielensis) were used for the microbiological studies. The antimicrobial activity of nanoceria was investigated across a wide range of concentrations using three methods sequentially; the antimicrobial activity was studied by examining diffusion into agar, the serial dilution method was used to detect the minimum inhibitory and bactericidal concentrations, and, finally, gas chromatography with mass-selective detection was performed to study the inhibition of E. coli’s growth. To study the redox activity of different concentrations of nanocerium, we studied the intensity of chemiluminescence in the oxidation reaction of luminol in the presence of hydrogen peroxide. As a result of this study’s use of the agar diffusion and serial dilution methods followed by sowing, no significant evidence of antimicrobial activity was found. At the same time, in the current study of antimicrobial activity against E. coli strains using gas chromatography with mass spectrometry, the ability of nanoceria to significantly inhibit the growth and reproduction of microorganisms after 24 h and, in particular, after 48 h of incubation at a wide range of concentrations, 10−2–10−5 M (48–95% reduction in the number of microbes with a significant dose-dependent effect) was determined as the optimum concentration. A reliable redox activity of nanoceria coated with citrate was established, increasing in proportion to the concentration, confirming the oxidative mechanism of the action of nanoceria. Thus, nanoceria have a dose-dependent bacteriostatic effect, which is most pronounced at concentrations of 10−2–10−3 M. Unlike the effects of classical antiseptics, the effect was manifested from 2 days and increased during the observation. To study the antimicrobial activity of nanomaterials, it is advisable not to use classical qualitative and semi-quantitative methods; rather, the employment of more accurate quantitative methods is advised, in particular, gas chromatography–mass spectrometry, during several days of incubation.

Cerium Dioxide–Dextran Nanocomposites in the Development of a Medical Product for Wound Healing: Physical, Chemical and Biomedical Characteristics

“…Currently, there is an active search for optimal ways to create new wound-healing drugs with a better balance of regenerative and antimicrobial effect of a new type that does not cause antibiotic resistance. Great hopes are placed on nanocomposites based on cerium oxide nanoparticles [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], which is a rare earth metal with variable valence, coated with a polymer shell, dextran [ 50 , 51 , 52 , 53 , 54 ], which is widely used in medicine [ 67 , 68 , 69 ]. This complex seems to be an excellent combination for the development of a medical drug that effectively accelerates wound healing.…”

“…We used a modified methodology published in our earlier papers [ 35 , 39 ]. Cerium oxide nanoparticles coated with the polysaccharide dextran were synthesized by the following methods.…”

“…In the course of our previous studies, we proved that the antimicrobial effect of nanocrystalline cerium oxide sols using classical methods (diffusion into agar, serial dilution method) is not reasonable to study, since nano-cerium does not diffuse into agar and its mechanism of action does not comply with the standard rules of pharmacopoeia [ 35 ], which is actually associated with contradictory results of different researchers (there are works claiming that metals nanoparticles have a pronounced antimicrobial effect [ 33 , 59 , 60 , 61 , 62 , 63 ]; at the same time, there are many works in which the authors did not obtain such an effect [ 64 , 65 , 66 ]).…”

“…In the last five years, according to PubMed data from 2019 to 2024, there were 7066 papers published on nanoceria, almost double the number of publications in the previous 5 years. Most of the studies investigating the biological effects of nanoceria have shown its redox activity as well as regenerative and even antimicrobial and pro-regenerative effects [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. There are many problems in the synthesis of new groups of nanodrugs that have not been encountered before.…”