Veronica Lazar

Copper(II) Complexes with Ligands Derived from 4-Amino-2,3- dimethyl-1-phenyl-3-pyrazolin-5-one: Synthesis and Biological Activity

The synthesis of Cu(II) complexes derived from Schiff base ligands obtained by the condensation of 2-hydroxybenzaldehyde or terephtalic aldehyde with 4-amino-antipyrine (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) is presented. The newly prepared compounds were characterized by( 1)H-NMR, UV-VIS, IR and ESR spectroscopy. The determination of the antimicrobial activity of the ligands and of the complexes was carried out on samples of Escherichia coli, Klebsiella pneumoniae, Acinetobacter boumanii, Pseudomonas aeruginosa, Staphylococcus aureus and Candida sp. The qualitative and quantitative antimicrobial activity test results proved that all the prepared complexes are very active, especially against samples of Ps. aeruginosa, A. Boumanii, E. coli and S. aureus.

Prospects for new antimicrobials based on N,N-dimethylbiguanide complexes as effective agents on both planktonic and adhered microbial strains.

Metal-free N,N-dimethylbiguanidium acetate and novel complexes M(DMBG)(2)(CH(3)COO)(2).nH(2)O (M: Mn(II), Ni(II), Cu(II) and Zn(II)) were screened for their antimicrobial properties against Gram-positive (Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus), Gram-negative (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa) bacteria and fungal (Candida albicans) strains. The ability of compounds to inhibit the microbial adherence ability to the inert substratum as well as their cytotoxicity was also assessed. Our results are demonstrating that some of the tested compounds are exhibiting potent antimicrobial activity accompanied by low cytotoxicity on HeLa cells. The complexes were characterized using microanalytical, IR, EPR, (1)H NMR as well as UV-vis methods. The redox behaviour of complexes was investigated by cyclic voltammetry. The new derivative (HDMBG)(CH(3)COO) crystallizes in the monoclinic P2(1)/n space group as X-ray single-crystal data indicate.

Inhibitory Activity of

Undesired biofilm development is a major concern in many areas, especially in the medical field. The purpose of the present study was to comparatively investigate the antibiofilm efficacy of usnic acid, in soluble versus nanofluid formulation, in order to highlight the potential use of Fe3O4/oleic acid (FeOA) nanofluid as potential controlled release vehicle of this antibiofilm agent. The (+) -UA loaded into nanofluid exhibited an improved antibiofilm effect on S. aureus biofilm formation, revealed by the drastic decrease of the viable cell counts as well as by confocal laser scanning microscopy images. Our results demonstrate that FeOA nanoparticles could be used as successful coating agents for obtaining antibiofilm pellicles on different medical devices, opening a new perspective for obtaining new antimicrobial and antibiofilm surfaces, based on hybrid functionalized nanostructured biomaterials.

{\rm Fe}_{3} {\rm O}_{4}

Acute and chronic wounds represent a very common health problem in the entire world. The dermal wounds are colonized by aerobic and anaerobic bacterial and fungal strains, most of them belonging to the resident microbiota of the surrounding skin, oral cavity and gut, or from the external environment, forming polymicrobial communities called biofilms, which are prevalent especially in chronic wounds. A better understanding of the precise mechanisms by which microbial biofilms delay repair processes together with optimizing methods for biofilm detection and prevention may enhance opportunities for chronic wounds healing. The purpose of this minireview is to assess the role of polymicrobial biofilms in the occurrence and evolution of wound infections, as well as the current and future preventive and therapeutic strategies used for the management of polymicrobial wound infections.

/Oleic Acid/Usnic Acid—Core/Shell/Extra-Shell Nanofluid on S. aureus Biofilm Development

During the present study, we have evaluated magnetic chitosan as a potential drug delivery device, by specifically determining if chitosan could elute antibiotics in an active form that would be efficacious in inhibiting Staphylococcus aureus and Escherichia coli growth. We have demonstrated that the incorporation of cephalosporins of second, third and fourth generation into magnetic chitosan microspheres can possibly lead to an improved delivery of antibiotics in active forms, probably due to the inherent properties of chitosan.

Polymicrobial wound infections: Pathophysiology and current therapeutic approaches

OBJECTIVES Toothbrushes are rapidly contaminated with different microorganisms, which colonize the oral cavity and interdental spaces. This can represent a possible cause of infection or reinfection. In this study, the ozone experimental effect upon toothbrushes microflora was estimated microbiologically before and after saturation with ozone gas. METHODS Fifty used toothbrushes coming from children and adults were entered our study. Microorganisms were enumerated and identified. Bristles from each brush were soaked in ozone saturated PBS solution for 5, 10, 15, 20 and 30 min and the total microbial population was reassessed. RESULTS Counts of microorganisms isolated per brush varied between 10(2) and 10(7) CFU. Candida albicans was present in used toothbrushes. No obligate anaerobes were isolated. Members of Streptococcaceae family were regularly found (65.2%) belonging to the following species: Streptococcus pyogenes, S. mutans, S. mitis, S. oralis, S. sobrinus, S. viridans, S. salivarius, S. sanguis, Aerococcus viridans. A. viridans and S. mutans were more frequently isolated on children toothbrushes while Staphylococcus aureus and S. epidermidis were found on adults brushes. Escherichia coli, Pseudomonas sp. and Enterococcus sp., were also recovered. We found that the ozone treatment decreased gradually the microbial load. However, a bacterial re-growth was effective following short ozonation period. Decontamination was complete after an extended exposure to ozone for 30 min. CONCLUSIONS Ozone application was found to remove the toothbrushes bristles microbiota following conventional brushing. Maximum decontamination efficacy of ozone treatment was observed after 30 min while exposure for short time periods seems to be inefficient which probably reflect the low dose of ozone used in this study.

Improved antibacterial activity of cephalosporins loaded in magnetic chitosan microspheres

The new complexes M(DMBG)(2)(ClO(4))(2) (M:Mn, Ni, Cu and Zn; DMBG: N,N-dimethylbiguanide) have been synthesized and characterized by IR, EPR, (1)H NMR, (13)C NMR as well as electronic spectroscopy data. Complex [Ni(DMBG)(2)](ClO(4))(2).2DMF (DMF: N,N-dimethylformamide) crystallizes in the monoclinic P2(1)/c space group while [Cu(DMBG)(2)](ClO(4))(2) adopt monoclinic P21/c space group as X-ray single crystal data indicate. The redox behavior of complexes was investigated by cyclic voltammetry. The metal-free N,N-dimethylbiguanide and complexes exhibit specific anti-infective properties as demonstrated the low MIC values, a large antimicrobial spectrum and also inhibit the ability of Pseudomonas aeruginosa and Staphylococcus aureus strains to colonize the inert surfaces. The complexes exhibit also a low cytotoxicity levels on HeLa cells.

A quantitative approach to the effectiveness of ozone against microbiota organisms colonizing toothbrushes.

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

N,N-dimethylbiguanide complexes displaying low cytotoxicity as potential large spectrum antimicrobial agents.

Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles with the antimicrobial activity of three essential oils to obtain novel nanobiosystems that could be used as coatings for catheter pieces with an improved resistance to Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and biofilm development. The essential oils of ylang ylang, patchouli and vanilla were stabilized by the interaction with iron oxide@C14 nanoparticles to be further used as coating agents for medical surfaces. Iron oxide@C14 was prepared by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium. Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples surface strongly inhibited both the initial adherence of S. aureus cells (quantified at 24 h) and the development of the mature biofilm quantified at 48 h. Patchouli and ylang-ylang essential oils inhibited mostly the initial adherence phase of S. aureus biofilm development. In the case of K. pneumoniae, all tested nanosystems exhibited similar efficiency, being active mostly against the adherence K. pneumoniae cells to the tested catheter specimens. The new nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with anti-adherence and anti-biofilm properties.

Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization

The aims of this study were the development, characterization and bioevaluation of a novel biocompatible, resorbable and bio-active wound dressing prototype, based on anionic polymers (sodium alginate--AlgNa, carboximethylcellulose--CMC) and magnetic nanoparticles loaded with usnic acid (Fe₃O₄@UA). The antimicrobial activity was tested against Staphylococcus aureus grown in biofilms. The biocompatibility testing model included an endothelial cell line from human umbilical vein and human foetal progenitor cells derived from the amniotic fluid, that express a wide spectrum of surface molecules involved in different vascular functions and inflammatory response, and may be used as skin regenerative support. The obtained results demonstrated that CMC/Fe₃O₄@UA and AlgNa/Fe₃O₄@UA are exhibiting structural and functional properties that recommend them for further applications in the biomedical field. They could be used alone or coated with different bio-active compounds, such as Fe₃O₄@UA, for the development of novel, multifunctional porous materials used in tissues regeneration, as antimicrobial substances releasing devices, providing also a mechanical support for the eukaryotic cells adhesion, and exhibiting the advantage of low cytotoxicity on human progenitor cells. The great antimicrobial properties exhibited by the newly synthesized nano-bioactive coatings are recommending them as successful candidates for improving the implanted devices surfaces used in regenerative medicine.