Carmen Chifiriuc

Hybrid magnetite nanoparticles/Rosmarinus officinalis essential oil nanobiosystem with antibiofilm activity

Biofilms formed by fungal organisms are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence of the fungi despite antifungal therapy. The purpose of this study is to combine the unique properties of nanoparticles with the antimicrobial activity of the Rosmarinus officinalis essential oil in order to obtain a nanobiosystem that could be pelliculised on the surface of catheter pieces, in order to obtain an improved resistance to microbial colonization and biofilm development by Candida albicans and C. tropicalis clinical strains. The R. officinalis essential oils were extracted in a Neo-Clevenger type apparatus, and its chemical composition was settled by GC-MS analysis. Functionalized magnetite nanoparticles of up to 20 nm size had been synthesized by precipitation method adapted for microwave conditions, with oleic acid as surfactant. The catheter pieces were coated with suspended core/shell nanoparticles (Fe3O4/oleic acid:CHCl3), by applying a magnetic field on nanofluid, while the CHCl3 diluted essential oil was applied by adsorption in a secondary covering treatment. The fungal adherence ability was investigated in six multiwell plates, in which there have been placed catheters pieces with and without hybrid nanoparticles/essential oil nanobiosystem pellicle, by using culture-based methods and confocal laser scanning microscopy (CLSM). The R. officinalis essential oil coated nanoparticles strongly inhibited the adherence ability and biofilm development of the C. albicans and C. tropicalis tested strains to the catheter surface, as shown by viable cell counts and CLSM examination. Due to the important implications of Candida spp. in human pathogenesis, especially in prosthetic devices related infections and the emergence of antifungal tolerance/resistance, using the new core/shell/coated shell based on essential oil of R. officinalis to inhibit the fungal adherence could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with antibiofilm properties.

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.

Water dispersible cross-linked magnetic chitosan beads for increasing the antimicrobial efficiency of aminoglycoside antibiotics

The aim of this study was to obtain a nano-active system to improve antibiotic activity of certain drugs by controlling their release. Magnetic composite nanomaterials based on magnetite core and cross-linked chitosan shell were synthesized via the co-precipitation method and characterized by Fourier transform infrared spectroscopy (FT-IR), infrared microscopy (IRM), scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The prepared magnetic composite nanomaterials exhibit a significant potentiating effect on the activity of two cationic (kanamycin and neomycin) drugs, reducing the amount of antibiotics necessary for the antimicrobial effect. The increase in the antimicrobial activity was explained by the fact that the obtained nanosystems provide higher surface area to volume ratio, resulting into higher surface charge density thus increasing affinity to microbial cell and also by controlling their release. In addition to the nano-effect, the positive zeta potential of the synthesized magnetite/cross-linked chitosan core/shell magnetic nanoparticles allows for a more favorable interaction with the usually negatively charged cell wall of bacteria. The novelty of the present contribution is just the revealing of this synergistic effect exhibited by the synthesized water dispersible magnetic nanocomposites on the activity of different antibiotics against Gram-positive and Gram-negative bacterial strains. The results obtained in this study recommend these magnetic water dispersible nanocomposite materials for applications in the prevention and treatment of infectious diseases.

Improved antibacterial activity of cephalosporins loaded in magnetic chitosan microspheres

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.

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

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.

Magnetic Properties and Biological Activity Evaluation of Iron Oxide Nanoparticles

The aim of this study was to provide information about the biological properties of iron oxide nanoparticles (IO-NPs) obtained in an aqueous suspension. The IO-NPs were characterized by transmission electron microscopy (TEM). Analysis of hysteresis loops data at room temperature for magnetic IO-NPs sample indicated that the IO-NPs were superparamagnetic at room temperature. The calculated saturation magnetization for magnetic iron oxide was = 18.1 emu/g. The antimicrobial activity of the obtained PMC-NPs was tested against Gram-negative (Pseudomonas aeruginosa 1397, Escherichia coli ATCC 25922), Gram-positive (Enterococcus faecalis ATCC 29212, Bacillus subtilis IC 12488) bacterial as well as fungal (Candida krusei 963) strains. The obtained results suggested that the antimicrobial activity of IO-NPs is dependent on the metallic ions concentrations and on the microbial growth state, either planktonic or adherent. The obtained IO-NPs exhibited no cytotoxic effect on HeLa cells at the active antimicrobial concentrations.

Fabrication, characterization and in vitro profile based interaction with eukaryotic and prokaryotic cells of alginate–chitosan–silica biocomposite

This work is focused on the fabrication of a new drug delivery system based on polyanionic matrix (e.g. sodium alginate), polycationic matrix (e.g. chitosan) and silica network. The FT-IR, SEM, DTA-TG, eukaryotic cell cycle and viability, and in vitro assay of the influence of the biocomposite on the efficacy of antibiotic drugs were investigated. The obtained results demonstrated the biocompatibility and the ability of the fabricated biocomposite to maintain or improve the efficacy of the following antibiotics: piperacillin-tazobactam, cefepime, piperacillin, imipenem, gentamicin, ceftazidime against Pseudomonas aeruginosa ATCC 27853 and cefazolin, cefaclor, cefuroxime, ceftriaxone, cefoxitin, trimethoprim/sulfamethoxazole against Escherichia coli ATCC 25922 reference strains.

Fabrication, characterization, and antimicrobial activity, evaluation of low silver concentrations in silver-doped hydroxyapatite nanoparticles

The aim of this study was the evaluation of (Ca10-xAgx)(PO4)6(OH)2 nanoparticles (Ag:HAp-NPs) for their antibacterial and antifungal activity. Resistance to antimicrobial agents by pathogenic bacteria has emerged in the recent years as a major public health problem worldwide. In this paper, we report a comparison of the antimicrobial activity of low concentrations silver-doped hydroxyapatite nanoparticles. Thesilver-doped nanocrystalline hydroxyapatite powderwas synthesized at 100°C indeionisedwater. The as-prepared Ag:Hap nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), FT-IR, and FT-Raman spectroscopy. X-ray diffraction (XRD) studies demonstrate that powders obtained by coprecipitation at 100°C exhibit the apatite characteristics with good crystal structure, without any new phase or impurities found. FT-IR and FTRaman spectroscopy revealed the presence of the various vibrational modes corresponding to phosphates and hydroxyl groups and the absence of any band characteristic to silver. The specific microbiological assays demonstrated that Ag:HAp-NPs exhibited antimicrobial features, but interacted differently with the Gram-positive, Gram-negative bacterial and fungal tested strains.

Tunable ZnO spheres with high anti-biofilm and antibacterial activity via a simple green hydrothermal route.

A family of distinct ZnO morphologies - hollow, compartmented, core-shell and full solid ZnO spheres, dispersed or interconnected - is obtained by a simple hydrothermal route, in the presence of the starch biopolymer. The zinc-carbonaceous precursors were characterized by infrared spectroscopy, thermal analysis and scanning electron microscopy, while the ZnO spheres, obtained after the thermal processing, were investigated by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, UV-VIS spectroscopy, photoluminescence measurements, antimicrobial, anti-biofilm and flow cytometry tests. The formation mechanism proposed for this versatile synthesis route is based on the gelling ability of amylose, one of the starch template constituents, responsible for the effective embedding of zinc cations into starch prior to its hydrothermal carbonization. The simple variation of the raw materials concentration dictates the type of ZnO spheres. The micro-sized ZnO spheres exhibit high antibacterial and anti-biofilm activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) reference and methicillin resistant clinical strains especially for Gram-negative biofilms (P. aeruginosa), demonstrating great potential for new ZnO anti-biofilm formulations.

Prevention of microbial biofilms - the contribution of micro and nanostructured materials.

Microbial biofilms are associated with drastically enhanced resistance to most of the antimicrobial agents and with frequent treatment failures, generating the search for novel strategies which can eradicate infections by preventing the persistent colonization of the hospital environment, medical devices or human tissues. Some of the current approaches for fighting biofilms are represented by the development of novel biomaterials with increased resistance to microbial colonization and by the improvement of the current therapeutic solutions with the aid of nano (bio)technology. This special issues includes papers describing the applications of nanotechnology and biomaterials science for the development of improved drug delivery systems and nanostructured surfaces for the prevention and treatment of medical biofilms. Nanomaterials display unique and well-defined physical and chemical properties making them useful for biomedical applications, such as: very high surface area to volume ratio, biocompatibility, biodegradation, safety for human ingestion, capacity to support surface modification and therefore, to be combined with other bioactive molecules or substrata and more importantly being seemingly not attracting antimicrobial resistance. The use of biomaterials is significantly contributing to the reduction of the excessive use of antibiotics, and consequently to the decrease of the emergence rate of resistant microorganisms, as well as of the associated toxic effects. Various biomaterials with intrinsic antimicrobial activity (inorganic nanoparticles, polymers, composites), medical devices for drug delivery, as well as factors influencing their antimicrobial properties are presented. One of the presented papers reviews the recent literature on the use of magnetic nanoparticles (MNP)-based nanomaterials in antimicrobial applications for biomedicine, focusing on the growth inhibition and killing of bacteria and fungi, and, on viral inactivation. The anti-pathogenic activity of the most common types of metallic/metal oxide nanoparticles, as well as the photocontrolled targeted drug-delivery system and the development of traditional Chinese herbs nanoparticles are some of the highlights of another paper of this issue. The applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization are also discussed, as well as one of the most recent paradigms of the pharmaceutical field and nanobiotechnology, represented by the design of smart multifunctional polymeric nanocarriers for controlled drug delivery. These systems are responding to physico-chemical changes and as a result, they can release the active substances in a controlled and targeted manner. The advantages and limitations of the main routes of polymerization by which these nanovehicles are obtained, as well as the practical appllications in the field of drug nanocarriers are presented. The authors describe the therapeutic applications of dendrimers, which are unimolecular, monodisperse nanocarriers with unique branched tree-like globular structure. The applications of nanotechnology for the stabilization and improved release of anti-pathogenic natural or synthetic compounds, which do not interfere with the microbial growth, but inhibit different features of microbial pathogenicity are also highlighted. We expect this special issue would offer a comprehensive update and give new directions for the design of micro/nano engineered materials to inhibit microbial colonization on the surfaces or to potentiate the efficiency of the current/ novel/alternative antimicrobial agents by improving their bioavailability and pharmacokinetic features.