Prolonged use of antibiotics can cause toxicity in human and animal cells and lead to the development of antibiotic resistance. The development of drug delivery systems for enhanced antibacterial properties of antibiotics could reduce toxic effects and minimize the development of resistance. The aim of this study was to evaluate the effectiveness of oxytetracycline in complexes with new polyphosphate ester-type transporters and to investigate the antimicrobial effect of these complexes on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth in vitro. Two polyphosphate ester-type transporters with different molecular weights were synthesized, and oxytetracycline was attached through the phosphorus groups. To determine the sensitivities of microorganisms, oxytetracycline hydrochloride and oxytetracycline complexes with polyphosphate ester-type transporters (P4 and P6) were added to liquid and solid media with E. coli, P. aeruginosa, and S. aureus in different doses. Oxytetracycline in complex with polyphosphate ester-type transporters at low doses (2.3 to 3.8 μg/disk or μg/mL) in both solid and liquid media inhibits the growth of S. aureus more effectively than oxytetracycline alone. The maximum influence on E. coli growth on solid media is observed at a dose of 8 μg/disk of oxytetracycline in combination with both P4 and P6 polyphosphate ester-type transporters. P. aeruginosa growth under the influence of oxytetracycline in combination with polyphosphate-ester type transporters in a liquid medium depends on the dose of antibiotic and the day of cultivation.

Amoxicillin is one of the most widely used antibacterial drugs. It is known to be the first reason of adverse effects caused by medications in human and animals. Antibacterial drugs, combined with a delivery agent, could provide desirable therapeutic effects with decreased toxicity and reduce the emergence of antimicrobial resistant bacteria. The aim of this study was to compare the toxicity of amoxicillin, polyphosphate ester amoxicillin complex and phosphate ester on mice. Synthesis of the polyphosphate ester (P4) was performed via polycondensation technique, using PEG-400. Animal studies were performed in accordance with the European Convention for the Protection of Vertebrate Animals (Strasbourg, 1986). BALB/c mice were treated by intramuscular injection with saline 0.2 mL (control), amoxicillin 0.2 mL (15 mg/kg); polyphosphate ester complex with amoxicillin 0.2 mL (with amoxicillin content 15 mg/kg) and polyphosphate ester 0.2 mL. Blood biochemical analysis and histology of liver, spleen and kidney were used to assess toxicity. Blood biochemical analysis indicates that P4 did not induce changes in liver and kidneys. Specifically, blood biochemical indicis that represent functional state and cell structure of these organs were within normal physiological values: ALT (56 ± 15.96 U/L), AST (265 ± 37.50U/L), urea (4.4 ± 1.45 mmol/L), creatinine 62.8 ± 5.17 mmol/L, cholesterol 3.5 ± 0.56 mmol/L, total protein 55.9 ± 4.60 g/L, glucose 8.1 ± 0.55 mmol/L. However, the analysis of organ to body weight ratio showed decreased liver ratio (p ≤ 0.05) in mice injected with polyphosphate ester (P4). Histological examination of the liver didn’t show severe pathological changes. There were single places with mild portal vein inflammation in liver of mice receiving amoxicillin and amoxicillin complexed with polyphosphate ester. P4 separately in some places caused cell cytoplasm granulation in liver. No spleen alterations were observed. Overall, the results of this study showed that P4 polyphosphate ester alone and in complex with amoxicillin does not cause renal, hepatic and splenic toxicity in mice. Thus, polyphosphate ester P4 can serve as a safe drug carrier for antimicrobial drugs. It is planned to carry out more extensive studies on other animal species to study its biocompatibility and effectiveness of antimicrobial activity in a complex with antimicrobials.

Vaccination is one of the main methods for the specific prevention of infectious diseases. The disadvantage of vaccination is the use of pathogens (live or attenuated viruses and bacteria) that can lead to the development of a disease. Recombinant technologies are capable of producing specific DNA or protein molecules that possess antigenic properties and do not cause disease. However, individual antigen molecules are low-immunogenic, and therefore, require conjugation with a compound possessing stronger immunogenic properties. In this study, we examined the immunogenic properties of the new anionic copolymer consisting of glycidyl methacrylate, butyl acrylate, triethylene glycol dimethacrylate, and acrylic acid, in mice. The experimental polymer induced a stronger immunogenic response than aluminum hydroxide. The histological studies have established that immunization both with aluminum hydroxide and the polymer studied does not cause damage to the liver, kidneys, or the spleen. No negative side effects were observed. It has been concluded that the new synthetic anionic polyelectrolyte hydrogel (PHG) has a potential as an adjuvant for vaccine development.

Background. Polyethylene glycol (PEG) is able to affect the permeability of memb­ra­nes by increasing the entry of antibiotics into the cell of microorganism; therefore, PEGylation may improve the effectiveness of antibiotics due to chemical modification of their molecules. It is important to assess the safety and toxicity of new compounds for drug development activity. The aim of this research was to study the functional state and structure of the kidneys of laboratory rats after intramuscular administration of PEGylated antibiotic enrofloxacin, as well as commercial antibiotic enrofloxacin and polymer PEG-400, which were used for the synthesis of PEGylated antibiotic enrofloxacin. Materials and Methods. PEGylated antibiotic enrofloxacin was obtained via the reaction between enrofloxacin chloride and PEG-400 polymer (polyethylene glycol with a molecular weight of 400 Da). The research was conducted on four groups of rats: control and three experimental ones, 12 animals in each group. Physiological saline solution was intramuscularly injected to the control rats; commercial antibiotic enrofloxacin – to rats of the first experimental group; polymer PEG-400 – to rats of the second experimental group; PEGylated antibiotic enrofloxacin – to rats of the third experimental group. Results. The conducted studies did not show a significant difference between the serum creatinine in control rats and experimental ones on the 7th, 14th and 21st days after the last administration of the drugs. Creatinine levels in the blood of all groups of animals were within physiological ranges. Histological studies of the kidney structure in control rats indicated no changes during the experiment. Histological changes in the structure of the kidneys were observed within the first seven days after the end of the intramuscular administration of polymer PEG-400 and PEGylated antibiotic enrofloxacin. Injections of the commercial form of antibiotic enrofloxacin to experimental rats caused histological changes in the kidney structure for 21 days of the experiment. Conclusions. Quadruple intramuscular administration of PEGylated and commercial antibiotics enrofloxacin to rats showed that PEGylation reduces nephrotoxicity and shortens the duration of adverse effects in the kidneys.

A reinforced pectin-based dressing with a reinforcing element containing the antimicrobial agent chlorhexidine bigluconate has been developed. In vitro studies have shown that the hydrogel pectin dressing containing 0.03 ÷ 1.5 % chlorhexidine bigluconate inhibits the growth of both gram-positive (S. aureus) and gram-negative (P. aeruginosa) bacteria. The dressing can be used in the complex treatment of postoperative wounds with infectious-inflammatory process. The efficacy of different doses of chlorhexidine bigluconate was characterized by growth inhibition and increase of microorganism-free areas on the culture medium around the site of dressing localization, and regardless of the type of bacteria. Bacterial growth inhibition radius size depends on the dose of chlorhexidine in the hydrogel pectin dressing. The inhibition of growth of S. aureus and P. aeruginosa is directly proportional to chlorhexidine bigluconate content. The increase of dressing saturation with chlorhexidine to 1.0 and 1.5 % recorded the maximum inhibition of the growth of microorganisms. A veterinary clinical trial has shown a good therapeutic effect in the wound healing, in particular in the complex treatment of postoperative and accidental wounds both in the presence of infectious-inflammatory process and in its absence. The reinforced pectin-based dressing with cotton (or polypropylene) reinforcement element containing chlorhexidine bigluconate reduces the cost of dressings and bandaging frequency during wound healing. It protects the wound surface from contamination, mechanical irritation, bacterial contamination and the development of secondary infection. The dressing promotes good water, air and heat exchange between the wound and the environment, adsorbs excess exudate, maintains a moist environment and does not cause hyperosmotic damage and drying of the wound. Surgical wound healing occurred under the initial tension for 7 days. Considering the method of its application, this dressing is suitable for use on different parts of the animal's body (neck, withers, chest and abdomen, lower back, buttocks, thighs, shoulders, etc.).