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The growing resistance of bacteria to antibiotics is one of the main public health problems nowadays. The influence of silver nanoparticle (AgNP) pretreatment of 220 cows with mastitis on the susceptibility of Staphylococcus epidermidis bacteria to 31 antibiotics was studied. The obtained results were compared with the previous results for Escherichia coli , Streptococcus dysgalactiae , and Staphylococcus aureus . For all four bacteria, an increase in susceptibility (9.5-21.2%) to 31 antibiotics after cow treatment with AgNPs was revealed, while after first-line antibiotic drug treatment as expected, the susceptibility decreased (11.3-27.3%). These effects were explained by (1) the increase in the contribution of isolates with efflux effect after antibiotic treatments and its decrease after AgNP treatment and (2) the changes in bacteria adhesion and anti-lysozyme activity after these treatments. The effect of the increasing antibacterial activity of antibiotics after AgNP treatment was the most pronounced in the case of E. coli and was minimal in the case of S. epidermidis . With AgNP treatment, the time of recovery decreased by 26.8-48.4% compared to the time of recovery after treatment with the first-line antibiotic drugs. The AgNP treatment allows for achieving the partial restoration of the activity of antibiotics.

The aerosol inhalation delivery of composite particles consisting of Ag nanoparticles enveloped by polyvinylpyrrolidone was investigated in experiments with mice. An ultrasonic nebulizing system was created for the generation of aerosols with a mean diameter and mass concentration of 700 ± 50 nm and 65 ± 5 mg/m 3 , respectively. The mass fraction of Ag in the composite particles was α = 0.061. The aerosol delivery was performed in a whole-body chamber with an exposition time of 20 min. Pharmacokinetic measurements were taken and the silver concentrations in the blood and lungs of the mice were measured as a function of time after exposition by means of electrothermal (graphite furnace) atomic absorption spectrometry. The inhalation dose and other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized silver was assessed for mice infected with Klebsiella pneumoniae 82 and Staphylococcus aureus ATCC 25953 . The survival rate of the infected mice after the aerosol exposure demonstrated the high antibacterial efficiency of Ag nanoparticles after inhalation delivery.

The increase in bacterial resistance to antibiotics is a global problem for public health. In our previous works, it was shown that the application of AgNPs in cow mastitis treatment increased S. aureus and S . dysgalactiae susceptibility to 31 antibiotics due to a decrease in the bacterial efflux effect. The aim of the present work was to shed light on whether the change in adhesive and anti-lysozyme activities caused by AgNPs also contribute to the restoration of bacterial susceptibility to antibiotics. In vivo sampling was performed before and after cow mastitis treatments with antibiotics or AgNPs. The isolates were identified, and the adhesive and anti-lysozyme activities were assessed. These data were compared with the results obtained for in vitro pre-treatment of reference bacteria with AgNPs or antibiotics. The present study revealed that bacterial treatments in vitro and in vivo with AgNPs: (1) decrease the bacterial ability to adhere to cells to start an infection and (2) decrease bacterial anti-lysozyme activity, thereby enhancing the activity of lysozyme, a natural "antibiotic" present in living organisms. The obtained data contribute to the perspective of the future application of AgNPs for recovering the activity of antibiotics rapidly disappearing from the market.

The current work is a continuation of our studies focused on the application of nanoparticles of metallic silver (AgNPs) to address the global problem of antibiotic resistance. In vivo, fieldwork was carried out with 200 breeding cows with serous mastitis. Ex vivo analyses showed that after the cow was treated with an antibiotic-containing drug Dienomast TM , E. coli sensibility to 31 antibiotics decreased by 27.3%, but after treatment with AgNPs, it increased by 21.2%. This could be explained by the 8.9% increase in the portion of isolates showing an efflux effect after Dienomast TM treatment, while treatment with Argovit-C TM resulted in a 16.0% drop. We verified the likeness of these results with our previous ones on S. aureus and Str. dysgalactiae isolates from mastitis cows processed with antibiotic-containing medicines and Argovit-C TM AgNPs. The obtained results contribute to the recent struggle to restore the efficiency of antibiotics and to preserve the wide range of antibiotics on the world market.

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/cm 3 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.

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 LC TM , S. dysgalactiae susceptibility to 31 antibiotics dropped by 22.9%, but after treatment with Argovit-C TM 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-C TM AgNPs was shown. So, mastitis treatments with Argovit-C TM 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.

Aerosol inhalation delivery of cefazolin, a broad-spectrum first-generation cephalosporin antibiotic, was investigated. Inhalation system based on ultrasonic nebulizer was developed for the generation of dry cefazolin aerosol within mean particle diameter range 0.5-3.0 μm and mass concentration 0.01-3 μg/cm 3 . Pharmacokinetic measurements were carried out for the aerosolized form of cefazolin delivered in mice using nose-only chamber. Cefazolin concentrations in blood serum and in the lungs of mice were measured as a function of time by means of high performance liquid chromatography. Body-delivered dose depending on particle size, concentration and inhalation time as well as other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized cefazolin was assessed through the aerosol inhalation treatment of mice infected with Klebsiella pneumoniae. Survival rate for infected mice after the treatment with cefazolin aerosol demonstrated high antibacterial efficiency of the inhalation delivery of cefazolin in comparison with intraperitoneal delivery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The effect of yeast double-stranded RNA (dsRNA) and of hyaluronic acid (HA) compositions produced on the interferon synthesis, peritoneal phagocytic activity of macrophages and on the hematological parameters were studied in an experiment with white noninbred mice. HA was shown to enhance the dsRNA-induced interferon synthesis, to inhibit the leukopenic reaction and to produce no effect on the phagocytosis-stimulating activity. The data obtained are indicative of that HA is a promising preparation regarding its use within the interferon-inducing compositions based on dsRNA.