Saltanat Jumabayeva

Background: Antimicrobial resistance (AMR) is among the most pressing challenges in modern infectious medicine, driving progressive failure of standard antibacterial therapy and rising mortality from infections caused by multidrug-resistant (MDR) pathogens. Antibiotic potentiation through adjuvant compounds capable of restoring the activity of existing drugs represents a promising strategy to overcome resistance without developing fundamentally new antibacterial molecules. This study aimed to evaluate the antibiotic-potentiating activity of a dextrin/polyvinyl alcohol/iodine complex (D/PVA/I-1), developed at the Scientific Center for Anti-Infectious Drugs JSC (Almaty, Kazakhstan), against clinically relevant MDR reference strains. Methods: Nine reference strains, Staphylococcus aureus (ATCC 33591, BAA-39), Escherichia coli (ATCC BAA-196, BAA-2523), Klebsiella pneumoniae (ATCC BAA-2524, 700603), Acinetobacter baumannii (ATCC BAA-1790), Streptococcus pneumoniae (ATCC BAA-660), and Haemophilus influenzae (ATCC 33930), and two clinical isolates, P. aeruginosa SCAID PHRX1-2019 and E. coli SCAID WND1-2021, were tested. Antibiotic-potentiating activity was assessed by checkerboard assay with calculation of the fractional inhibitory concentration index (FICI); bactericidal kinetics were evaluated by time-kill analysis. The effect of D/PVA/I-1 on cytoplasmic membrane permeability was investigated using a crystal violet uptake assay. Results: Of 45 D/PVA/I-1–antibiotic combinations tested across nine antibiotics, synergy (FICI ≤ 0.5) was demonstrated in 44.4% of cases, partial synergy in 48.9%, and additive effects in 6.7%; no antagonistic interactions were detected. The most pronounced potentiating effect occurred against Gram-positive pathogens, particularly MRSA strains (66.7% synergistic combinations). Time-kill analysis confirmed suppression of the regrowth phenotype characteristic of MDR strains under monotherapy and restoration of bactericidal activity against antibiotics to which strains exhibited intrinsic resistance. D/PVA/I-1 induced a dose- and time-dependent increase in membrane permeability in both Gram-positive and Gram-negative organisms. Conclusions: D/PVA/I-1 is an effective broad-spectrum antibiotic potentiator and represents a promising basis for combination therapy regimens against MDR infections.

Iodine-based antimicrobial materials are widely considered for biomedical applications due to their broad-spectrum antimicrobial activity; however, their potential genotoxicity requires systematic evaluation prior to clinical use. The aim of this study was to assess the genotoxic potential of a dextrin–polyvinyl alcohol–iodine (D/PVA/I-1) complex in accordance with OECD guidelines. Genotoxicity was evaluated in vitro using two complementary assays: the mammalian cell micronucleus test (OECD TG 487) in L5178Y TK^+/− cells and the bacterial reverse mutation assay (Ames test, OECD TG 471) using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA, both in the presence and absence of metabolic activation (S9). In the micronucleus assay, no statistically significant increase in micronucleus frequency was observed at concentrations ranging from 0.039 to 0.625 mg/mL compared with the negative control. In the Ames test, no increase in revertant colony numbers was detected in any tested bacterial strain at concentrations up to 1250 μg/plate. At higher concentrations, pronounced cytotoxic and bactericidal effects were observed without evidence of mutagenic activity. Overall, the results demonstrate that the D/PVA/I-1 complex does not exhibit genotoxic or mutagenic potential under the tested in vitro conditions, indicating a favorable genetic safety profile and supporting further preclinical evaluation for potential biomedical applications.

Background: Iodine-based antimicrobial systems remain highly attractive due to their broad-spectrum activity; however, the clinical application of free iodine is limited by its instability and cytotoxicity. This study aimed to develop polyethylene glycol (PEG)-based hydrophilic ointment formulations containing a dextrin/polyvinyl alcohol/iodine complex (D/PVA/I) and to evaluate their physicochemical properties, antimicrobial activity, and cytotoxicity. Methods: Hydrophilic ointment formulations containing 2.5%, 5.0%, and 10.0% D/PVA/I were prepared using a PEG-based matrix composed of PEG 4000, PEG 400, and glycerol. Physicochemical characterization included organoleptic evaluation, pH measurement, rheological analysis, and UV–visible (Ultraviolet–visible) spectroscopy. Antimicrobial activity was assessed using agar diffusion and minimum bactericidal concentration (MBC) assays against Staphylococcus aureus, Escherichia coli, Enterococcus hirae, and Pseudomonas aeruginosa. Cytotoxicity was evaluated in Madin–Darby Canine Kidney (MDCK) cells using the MTT assay. Results: All formulations exhibited homogeneous semisolid structure and physiologically acceptable pH values (4.94–5.45). Rheological analysis demonstrated non-Newtonian pseudoplastic (shear-thinning) behavior. The flow behavior index (n) ranged from 0.03 to 0.33 according to the Ostwald–de Waele model, confirming shear-thinning characteristics, while viscosity increased with increasing D/PVA/I concentration. UV–visible spectroscopy confirmed the presence of triiodide ions (I_3⁻), characterized by absorption maxima at approximately 287 and 350 nm, indicating preservation of active iodine species within the PEG matrix, while placebo (blank) formulation analysis confirmed the absence of corresponding absorption bands, demonstrating that the PEG-based matrix does not contribute to the characteristic spectral features. The formulations demonstrated broad-spectrum antimicrobial activity, with MBC values ranging from 0.01 to 0.02 µg/mL. Cytotoxicity studies revealed moderate toxicity of the D/PVA/I complex (CC₅₀ = 0.82%) (50% cytotoxic concentration (CC₅₀) and significantly lower toxicity of the PEG-based ointment base (CC₅₀ = 18.38%). Conclusions: The developed PEG-based hydrophilic ointment formulations containing the D/PVA/I complex demonstrated favorable physicochemical characteristics, stability of iodine species, pronounced antimicrobial activity, and acceptable cytotoxicity profiles. These findings highlight the potential for the developed systems to be promising topical antimicrobial formulations.

The global spread of multi-resistant pathogenic microorganisms has significantly complicated the treatment of chronic wounds. The development of novel drugs requires a substantial time investment. Hybrid materials such as nanoparticles stabilized by plant extracts are considered the best for creating efficient antiseptic substances. This paper is the first to discuss quantitative and qualitative analyses of the phytochemical constituents of the medicinal plant Artemisia terrae-albae, collected in Kazakhstan. The antimicrobial activity of the extracts, as well as of silver nanoparticles (AgNPs) stabilized by Artemisia terrae-albae extract, were evaluated. AgNPs were characterized by an average size of 82 nm or larger with a negative surface charge. TEM analysis of the obtained suspension showed a nonuniform structure of particles synthesized at a low concentration of ethyl acetate solvent in water. The SPR peak of AgNPs@Art aq. extract was detected at 420 nm, while any clear SPR peak was observed for AgNPs@Art ethylacetate extract. Diluted Artemisia terrae-albae extracts did not exhibit pronounced antimicrobial activity due to the poor solubility of compounds in water. Nevertheless, the AgNPs@Art aq. and AgNPs@Art EtAc. extracts possessed antimicrobial activity against the Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 6538, Escherichia coli (ATCC 8739), and Candida albicans ATCC 10231 strains.