The present work presents translational research with application of AgNPs targeting the global drug resistance problem. In vivo fieldwork was carried out with 400 breeding farm cows sick with a serous mastitis. Ex vivo results revealed that after cow treatment with LactobayTM (a mixture of antibiotic drugs) the susceptibility to 31 antibiotics of S. aureus isolates from cow breast secretion decreased by 25%, while after treatment with Argovit–CTM silver nanoparticles S. aureus susceptibility increased by 11%. The portion of isolates with an efflux effect leading to elimination of antibiotics from S. aureus after Lactobay-treatment resulted in a 15% increase, while Argovit-C-treatment led to a 17.5% decrease. The obtained results showed that mastitis treatments with Argovit-CTM AgNPs can partially restore the activity of antibiotics towards S. aureus and shorten the duration of mastitis treatment by 33%.

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The present work is a continuation of our translational research focusing on the use of silver nanoparticles (AgNPs) to solve the global problem of antibiotic resistance. In vivo fieldwork was done with 300 breeding farm cows with serous mastitis. Ex vivo assays revealed that after cow treatment with the antibiotic drug Spectromast LCTM, S.dysgalactiae susceptibility to 31 antibiotics dropped by 22.9%, but after treatment with Argovit–CTM AgNPs, it was raised by 13.1%. This was explained by the fact that the percentage of isolates with an efflux effect after Spectromast LC treatment resulted in an 8% increase, while Argovit-C-treatment caused a 19% decrease. The similarity of these results to our previous results on S. aureus isolates from mastitis cows treated with the antibiotic drug Lactobay and Argovit–CTM AgNPs was shown. So, mastitis treatments with Argovit-CTM AgNPs can partially return the activity of antibiotics towards S.dysgalactiae and S. aureus, while, in contrast, treatments with antibiotic drugs such as Spectromast LC and Lactobay enhance bacterial resistance to antibiotics. The results of this work strengthen the hope that in the future the use of AgNPs as efflux pump inhibitors will recover the activity of antibiotics, and thus will preserve the wide spectrum of antibiotics on the market.

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Aerosol inhalation delivery of ceftriaxone in mice was investigated. An ultrasonic nebulizer within the ranges of mean particle diameter 0.5–1.5 μm and mass concentration 0.01–0.6 μg/cm3 was used in inhalation experiments. Pharmacokinetic measurements were carried out using a nose-only chamber. Ceftriaxone concentration in blood serum and its mass in the lungs of mice were measured as a function of time using high-performance liquid chromatography. The body-delivered dose was within the range 3–5 mg/kg. The antibacterial effect of aerosolized ceftriaxone was investigated for mice infected with Klebsiella pneumoniae 82 and Staphylococcus aureus ATCC 25 953. The survival rate for infected mice after the treatment with ceftriaxone aerosol revealed the high antibacterial efficiency of this kind of treatment.

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Research has been conducted to evaluate the effect of antibiotics and silver nanoparticles in combination with antibiotics on the change in antibiotic sensitivity to antibacterial drugs of E. coli ATCC 25922 reference strain and its isolate. Nanoparticles obtained by electron beam treatment of aqueous solution containing water-soluble stabilizing polymer and water-soluble silver salt were used in the experiment. During the treatment a beam of accelerated electrons obtained on the installation of a linear accelerator of the ILU-10 type passed through a solution with a working dose of 5–30 kGy ranging in size from 20 to 60 nm. Sensitivity of microorganisms of E. coli ATCC 25922 reference strain and its isolate obtained from cow endometritis to antibacterial substances and their combinations was determined from dilution with a minimum bacteriostatic concentration. The dilution in the amount of 0.2 ml was added to meat-and-peptone agar and the antibiotic sensitivity of microorganisms was determined by the disk diffusion method. Sensitivity to 24 types of antibacterial drugs was tested. Cultivation of E. coli ATCC 25922 with AgNPs in combination with one of the antibiotics (azitronite, amoxicillin, enroflox, ceftiofur, tylosin, cobactan, oxytetracycline) contributed to an increase in the number of drugs (from 14.3 to 57.1%), to which the microorganism was sensitive. Cultivation of the E. coli isolate with 5 (62.5%) of the studied antibiotics led to an increase in resistance from 1 (5.5%) to 3 (16.7%) antibacterial agents. AgNPs in combination with antibiotics azitronite, amoxicillin, enroflox, ceftiofur, tylosin, cobactan, gentamicin, oxytetracycline contributed to a decrease in the resistance of E. coli ATCC 25922 (from 15.4 to 46.1%) and E. coli field isolate (from 16.7 to 37.7%) to antibacterial drugs. The pronounced ability of AgNPs to increase antibiotic sensitivity was established. This was confirmed by the joint cultivation of antibiotics and AgNPs with E. coli ATCC 25922 and field isolate of E. coli, causing an increase in sensitivity and high sensitivity to antibacterial drugs, which was previously absent. The study confirmed the results of research on the ability of nanoparticles of metals of the transition group to affect the sensitivity of microorganisms to antibacterial agents and to restore it.

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