Subchronic toxicity of silver nanoparticles stabilized by cetylperidinium anion as a potential antimastitis agent

Development of innovative antimastitis agents is a relevant direction in veterinary reproductology, as inflammatory diseases of the mammary gland have become widespread, especially in high-yielding animals. Among the newest agents with pronounced antimicrobial and anti-inflammatory effects, Silver nanoparticles are the most attractive. Their use as part of a complex drug for treatment of animals with mastitis will not only have high clinical efficacy, but also be a tool for combating biofilm formation and the problem of antibiotic resistance. However, the clinical use of Silver nanoparticles for productive animals requires the completion of a set of preclinical studies, in particular, the elucidation of their skin-resorptive and local-irritating effects. Therefore, the aim of the work was to determine the effect of Silver nanoparticles stabilized by cetylperidinium anion upon dermal application in different concentrations. The studies used 24 female rats and 18 doe rabbits. At the same time, rats were divided into 4 groups, to which a solution of the studied nanoparticles was applied to the shaved areas of the skin daily for 30 days, in particular, experimental group I – at a concentration of 0.05 g/L; experimental group II – 0.15 g/L; experimental group III – 0.45 g/L, while the rats of the control group received distilled water. The resorptive effect was assessed by the dynamics of changes in body weight, total leukocyte count, leukocyte profile on the 1st, 15th and 30th day of the experiment. The local irritant effect upon cutaneous application was determined using a previously shaved area on the right side measuring 5×5 cm, where nanoparticle solutions were evenly distributed in concentrations similar to those of experimental groups of rats, while the control was a shaved area of skin on the opposite side. The irritant effect on the mucous membranes of the eyes in rabbits was determined by a single application of two drops of nanoparticle solution into the lower conjunctival vault of the right eye, the control was the left eye, where a similar volume of distilled water was applied. The severity of the manifestation of pathological signs was assessed in points. The conducted studies established the absence of skin-resorptive effect of Silver nanoparticles in a subchronic experiment, in particular, in female rats, no changes in body weight were observed during 30 days after dermal application, the leukocyte profile did not have significant changes compared to the control. In experimental groups I and II, there were no changes in the number of leukocytes, and in experimental group III, an increase in this indicator by 16.0–17.9 % was noted. No allergic effect was detected during the scarification test. In rabbits, after dermal application and introduction of a solution of nanoparticles into the lower conjunctival vault, signs of irritation were not observed in any of the concentrations used. Thus, Silver nanoparticles stabilized by cetylperidinium anion are a safe substance that can be used as part of a complex antimastitis agent.