Katarzyna Zawadzka

Biological properties of new viologen-phosphorus dendrimers.

Some biological properties of eight dendrimers incorporating both phosphorus linkages and viologen units within their cascade structure or at the periphery were investigated for the first time. In particular cytotoxicity, hemotoxicity, and antimicrobial and antifungal activity of these new macromolecules were examined. Even if for example all these species exhibited good antimicrobial properties, it was demonstrated that their behavior strongly depends on several parameters as their size and molecular weight, the number of viologen units and the nature of the terminal groups.

Surface area or diameter – which factor really determines the antibacterial activity of silver nanoparticles grown on TiO2 coatings?

Titanium dioxide coatings were prepared on Si wafers using the sol–gel method. Four different types of coatings with silver nanoparticles (AgNPs) were synthesized. The diameter and surface density of AgNPs were conditioned by the concentration of Ag+ ions in the initial solution, time and UV illumination source. The bactericidal activity of AgNPs on the titanium dioxide coatings against the S. aureus strain were calculated as the percentage of the inhibition of bacterial growth after 24 hour incubation of microorganisms at 37 °C on TiO2 coatings with AgNPs. Control samples were coated with titanium dioxide without AgNPs. We concluded that the titanium dioxide coatings modified with silver nanoparticles had a high antibacterial activity. Moreover, we demonstrated strong dependence between surface areas of AgNPs and inhibition of bacterial growth. The obtained results evidence that the surface area of AgNPs grown on titanium dioxide coatings is a major factor determining their antimicrobial potential.

The antibacterial effect of the co-administration of poly(propylene imine) dendrimers and ciprofloxacin

Fluoroquinolones, including ciprofloxacin, are often used to treat bacterial diseases. Due to the spread of drug resistance among microorganisms, alternative treatments are being sought. We report here on the antimicrobial activity of generation 4 (G4) PPI dendrimers in the presence of ciprofloxacin against the reference strains of Gram-positive bacterium Staphylococcus aureus ATCC 6538 and Gram-negative bacterium Escherichia coli ATCC 25922. Cytotoxicity of these compounds was investigated in the eukaryotic B14 Chinese hamster fibroblast cell line, HepG2 human liver hepatocellular carcinoma cell line, mouse neuroblastoma N2a cell line and BRL-3A rat liver cell line. For both strains, the administration of PPI dendrimers along with ciprofloxacin significantly improved its antibacterial effect compared to the cultures given the drug alone. The simultaneous application of dendrimers and ciprofloxacin shows the opportunity of using it at lower doses. Ciprofloxacin and PPI dendrimers are harmful to bacterial strains at the concentrations non-toxic to the eukaryotic cells.

Enhancement of antimicrobial activity by co-administration of poly(propylene imine) dendrimers and nadifloxacin

Despite the studies of dendrimers for biomedical application, the antibacterial activity of dendrimers has not been extensively explored. In the presented study we evaluate the antimicrobial activity of poly(propylene imine) dendrimers (PPI-G4) and their derivatives modified with maltose (PPI-25%mG4) in combination with nadifloxacin against Gram-negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 15442 and Proteus hauseri ATCC 13315. Cytotoxicity of all studied dendrimers and nadifloxacin was investigated in a Chinese hamster fibroblast cell line (B14), a human liver hepatocellular carcinoma cell line (HepG2), a mouse neuroblastoma cell line (N2a) and a rat liver cell line (BRL-3A). The obtained results indicate that co-administration of nadifloxacin and studied dendrimers enhances the antimicrobial activity of the antibiotic against Gram-negative bacteria, at concentrations that are at the same time harmless to the eukaryotic cell lines. Moreover, the contribution of dendrimers allows using lower doses of the antibiotic.

Poly(Propylene Imine) Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin.

Antibacterial activity of high concentrations of carvedilol against Gram-positive and Gram-negative bacteria

Many drugs used to treat non-infectious diseases have also shown excellent antibacterial activity or the ability to enhance the action of antibiotics. The aim of this study was to investigate the antibacterial activity of a popular β-blocker, carvedilol, and its mechanism of antibacterial action. The antibacterial activity of carvedilol was evaluated using the microdilution method and its influence on the viability of bacterial cells was investigated by the alamarBlue® test. Changes in phospholipid and fatty acid composition were analysed using LC-MS/MS and GC-MS techniques. The permeability of bacterial cell membranes following exposure to carvedilol was studied using propidium iodide staining and confocal microscopy. The ability of the tested bacteria to degrade carvedilol was examined by LC-MS/MS. In this study, the antibacterial activity of carvedilol is described for the first time, with a decrease in the viability of all assayed bacteria observed following treatment with the β-blocker. Staphylococcus aureus and Staphylococcus epidermidis were found to be the most sensitive among the tested strains. Significant modifications to fatty acid composition were observed in S. aureus incubated with carvedilol. Moreover, the cell membrane permeability of bacteria incubated with carvedilol was higher for Gram-positive bacteria than for Gram-negative bacteria. Furthermore, Gram-negative Escherichia coli and Pseudomonas aeruginosa strains, which were highly resistant to carvedilol, exhibited an ability to eliminate carvedilol from the growth medium. In addition, three carvedilol metabolites were identified in E. coli and P. aeruginosa cultures. The antibacterial activity of carvedilol may suggest its potential usefulness in the synthesis of new antibacterial drugs.