Doroshenko A. Sorption and antimicrobial efficacy of composite of nanodispersed silica with polyhexamethylene guanidine hydrochloride

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0421U100776

Applicant for

Specialization

  • 14.03.05 - Фармакологія

01-04-2021

Specialized Academic Board

Д 64.605.03

National University of Pharmacy

Essay

The thesis is dedicated to theoretical and experimental substantiation of an expediency of development of a new combined drug with sorption and antimicrobial properties – a composite of nanodispersed silica with polyhexamethyleneguanidine hydrochloride. In determining the acute toxicity of the composite NDS+PGMG-HC, it was found that when applied topically at a dose of 2000 mg/kg with a content of PGMG-HC 20 % composite classified as toxicity class VI (according to Sidorov K. K.) – relatively harmless substances, and at intragastric administration in a dose of 2000 mg/kg with the content of NDS+PGMG-HC of 20 % – to the IV class of toxicity – low-toxic substances. High antimicrobial activity against planned forms of microorganisms is determined. The most sensitive to the composition of NDS+PGMG-HC were gram-positive microorganisms and fungi – MBC S. aureus and MFC C. albicans was 19.53 μg/ml (in terms of PGMG-HC). The least sensitive – gram-negative microorganisms – MBC E. coli and S. enterica was 39.06 μg/ml, K. pneumoniae and P. aeruginosa – 78.13 μg/ml (in terms of PGMG-HC). It was determined that the composite NDS+PGMG-HC at concentrations of 40 μg/ml and 90 μg/ml in terms of PGMG-HC inhibited the film formation of P. aeruginosa by 93.5 % and 92.1 %, respectively. Led to the destruction of 1-day biofilm at concentrations of 40 μg/ml and 90 μg/ml in terms of PGMG-HC by 74.3 % and 89.8 %, respectively, and 5-day by 72.3 % and 70.4 % in accordance. Planimetric studies confirmed morphological data and a reduction in the healing time of burn injury with the use of NDS+PGMG-HC composite – on the 28th day of the experiment, the reduction in wound area was 99.5 %, compared with 89 % in animals treated with chlorhexidine. On the 28th day of the experiment in all study groups, the burn wound was completely covered with newly formed epithelium, in some places there were foci of its dystrophy and hyperplasia. However, in the group of animals treated with the NDS+PGMG-HC composite, such destructive-proliferative changes were not observed. Proven antimicrobial, anti-inflammatory and wound-healing activity of the composite NDC+PGMG-HC in the treatment of animals with purulent abscess caused by Pseudomonas aeruginosa, which is confirmed by normalization of body weight on the 10th day of observation (in control remained reduced by 13 %) (P < 0,05), the absence of generalized infection (from blood samples of animals treated with NDS+PGMG-HC composite microorganisms were not sown) and morphological indicators – on the 12th day of treatment there was no area of necrosis, there was a pronounced suppression of inflammation, swelling in the areas adjacent to the abscess was insignificant , there was a germination of blood vessels to the central areas of infectious lesions, and collagen fibers were observed, which indicates the organization of the affected areas.

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