Michal Natan

Characterization and antibacterial properties of N-halamine-derivatized cross-linked polymethacrylamide nanoparticles

N-halamine-derivatized cross-linked polymethacrylamide nanoparticles with sizes ranging between 18 ± 2.0 and 460 ± 60 nm were prepared via surfactant-free dispersion co-polymerization of methacrylamide (MAA) and the cross-linking monomer N,N-methylenebisacrylamide (MBAA) in an aqueous continuous phase, followed by a chlorination process using sodium hypochlorite. The effect of various polymerization parameters (monomer concentration, initiator type and concentration, polymerization duration, polymerization temperature, and the weight ratio [MBAA]/[MAA]) on the size and size distribution of the produced cross-linked P(MAA-MBAA) nanoparticles was elucidated. The effect of various chlorination parameters (hypochlorite concentration, chlorination period and temperature) on the bound oxidative chlorine atom (Cl) content of the P(MAA-MBAA) nanoparticles was also investigated. The bactericidal activity of these chloramine-derivatized nanoparticles was tested against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus), and they were found to be highly potent. Furthermore, these nanoparticles also exerted their antimicrobial activity against multi-drug resistant (MDR) bacteria, further demonstrating their efficacy.

Killing Mechanism of Stable N-Halamine Cross-Linked Polymethacrylamide Nanoparticles That Selectively Target Bacteria

Increased resistance of bacteria to disinfection and antimicrobial treatment poses a serious public health threat worldwide. This has prompted the search for agents that can inhibit both bacterial growth and withstand harsh conditions (e.g., high organic loads). In the current study, N-halamine-derivatized cross-linked polymethacrylamide nanoparticles (NPs) were synthesized by copolymerization of the monomer methacrylamide (MAA) and the cross-linker monomer N,N-methylenebis(acrylamide) (MBAA) and were subsequently loaded with oxidative chlorine using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated remarkable stability and durability to organic reagents and to repetitive bacterial loading cycles as compared with the common disinfectant NaOCl (bleach), which was extremely labile under these conditions. The antibacterial mechanism of the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were not generated upon suspension in water, revealing that the mode of action is target-specific. Further, a unique and specific interaction of the chlorinated NPs with Staphylococcus aureus was discovered, whereby these microorganisms were all specifically targeted and marked for destruction. This bacterial encircling was achieved without using a targeting module (e.g., an antibody or a ligand) and represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl nanostructures. Our findings provide insights into the mechanism of action of P(MAA-MBAA)-Cl NPs and demonstrate the superior efficacy of the NPs over bleach (i.e., stability, specificity, and targeting). This work underscores the potential of developing sustainable P(MAA-MBAA)-Cl NP-based devices for inhibiting bacterial colonization and growth.

From Nano to Micro: using nanotechnology to combat microorganisms and their multidrug resistance

The spread of antibiotic resistance and increasing prevalence of biofilm-associated infections is driving demand for new means to treat bacterial infection. Nanotechnology provides an innovative platform for addressing this challenge, with potential to manage even infections involving multidrug-resistant (MDR) bacteria. The current review summarizes recent progress over the last 2 years in the field of antibacterial nanodrugs, and describes their unique properties, mode of action and activity against MDR bacteria and biofilms. Biocompatibility and commercialization are also discussed. As opposed to the more common division of nanoparticles (NPs) into organic- and inorganic-based materials, this review classifies NPs into two functional categories. The first includes NPs exhibiting intrinsic antibacterial properties and the second is devoted to NPs serving as a cargo for delivering antibacterial agents. Antibacterial nanomaterials used to decorate medical devices and implants are reviewed here as well.

Antibiotic nanoparticles embedded into the Parylene C layer as a new method to prevent medical device-associated infections

Tetracycline nanoparticles (NPs) were synthesized and simultaneously deposited on Parylene-C coated glass slides using ultrasound irradiation. The optimization of the process conditions, the specific reagent ratio and the precursor concentration resulted in the formation of uniform NPs with an average size of ∼50 nm. These novel tetracycline NP coated-surfaces were tested against two common bacterial pathogens, Escherichia coli and Staphylococcus aureus, and were found to be extremely potent against both bacteria, suggesting that these antibiotic NPs provide the Parylene surface with self-sterilizing properties. Finally, the mechanism describing the formation of tetracycline NPs and their subsequent deposition on the Parylene C surface is presented.

New Life for an Old Antibiotic

Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Staphylococcus aureus (S. aureus). The size and deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of π-π stacking between GO and TET additionally facilitate the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL but influences the biocidal activity of the GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications.

Engineering of Superparamagnetic Core–Shell Iron Oxide/N-Chloramine Nanoparticles for Water Purification

In this study, we describe the synthesis and characterization of superparamagnetic core-shell iron oxide (IO)/N-halamine antibacterial nanoparticles (NPs). For this purpose, superparamagnetic IO core NPs were coated with cross-linked polymethacrylamide (PMAA) by surfactant-free dispersion copolymerization of methacrylamide and N,N-methylenebis(acrylamide) in an aqueous continuous phase. The effect of the polymerization process on the chemical composition, size, shape, crystallinity, and magnetic properties of the IO/PMAA NPs was elucidated. Conversion of the core-shell IO/PMAA NPs into their N-halamine form, IO/PMAA-Cl, was accomplished using a chlorination reaction with sodium hypochlorite. The influence of chlorination on the shape, crystallinity, and magnetic properties of the IO/PMAA NPs was studied. The IO/PMAA-Cl NPs demonstrated excellent antibacterial activity against Gram-negative and Gram-positive bacteria. Finally, the chlorination recharging capabilities of the NPs and their potential for use in the purification of water containing bacteria were demonstrated with magnetic columns packed with the IO/PMAA-Cl NPs.

Biofilm prevention on cochlear implants

Abstract Objectives To examine the efficiency of a bacteria-resistant coating for the polydimethylsiloxane (PDMS) casing of cochlear implants. Methods The coatings are based on thin titania films that are made by liquid phase deposition or atomic layer deposition. The antibacterial activity of the coating was tested by two different detection assays: BCA protein and confocal microscopy. Results Coating the PDMS with thin films (10–40 nm) of titania significantly reduces the accumulation of bacteria. Discussion Thin oxide films made under conditions that do not undermine the integrity of polymeric materials can be used as anti-microbial coatings for soft polymers such as the PDMS that is used as a casing for cochlear implants or other medical devices.

Synthesis and characterization of fluoro-modified polypropylene films for inhibition of biofilm formation.

Surface hydroperoxide-conjugated polypropylene (PP) films were prepared by optimal ozonolysis processing of the films. These hydroperoxide-conjugated groups were then used as initiators at room temperature for redox graft polymerization of the fluoro vinylic monomer 1H,1H-heptaflourobutyl methacrylate (HFBM). The ozonolysis process allows, on one hand, for the formation of the desired hydroperoxide-conjugated groups while, on the other hand, leads to an undesired degradation of the PP. The ozone treatment time was therefore optimized to obtain sufficient hydroperoxide groups for graft polymerization, while maintaining the mechanical strength of the films, which was barely affected. The resulting PP-PolyHFBM (PP-PHFBM) films were characterized by methods such as AFM, ATR, TGA, contact angle goniometry and XPS. The antibiofilm properties of the PP-PHFBM films were evaluated, using two bacterial strains. An 86% inhibition was observed for the Gram-negative Escherichia coli, and a 37% inhibition was observed for the Gram-positive Listeria.

Ga@C-dots as an antibacterial agent for the eradication of Pseudomonas aeruginosa

The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This research article reports on the synthesis of gallium (Ga) doped in carbon (C)-dots (Ga@C-dots) and their antimicrobial activity against free-living P. aeruginosa bacteria. The synthesis of Ga@C-dots was carried out by sonicating molten Ga (for 2.5 h) in polyethylene glycol-400, which acts as both a medium and carbon source. The resultant Ga@C-dots, having an average diameter of 9±2 nm, showed remarkably enhanced antibacterial activity compared with undoped C-dots. This was reflected by the much lower concentration of Ga doped within Ga@C-dots which was required for full inhibition of the bacterial growth. These results highlight the possibility of using Ga@C-dots as potential antimicrobial agents.

Graft polymerization of styryl bisphosphonate monomer onto polypropylene films for inhibition of biofilm formation

There has been increased concern during the past few decades over the role bacterial biofilms play in causing a variety of health problems, especially since they exhibit a high degree of resistance to antibiotics and are able to survive in hostile environments. Biofilms consist of bacterial aggregates enveloped by a self-produced matrix attached to the surface. Ca(2+) ions promote the formation of biofilms, and enhance their stability, viscosity, and strength. Bisphosphonates exhibit a high affinity for Ca(2+) ions, and may inhibit the formation of biofilms by acting as sequestering agents for Ca(2+) ions. Although the antibacterial activity of bisphosphonates is well known, research into their anti-biofilm behavior is still in its early stages. In this study, we describe the synthesis of a new thin coating composed of poly(styryl bisphosphonate) grafted onto oxidized polypropylene films for anti-biofilm applications. This grafting process was performed by graft polymerization of styryl bisphosphonate vinylic monomer onto O2 plasma-treated polypropylene films. The surface modification of the polypropylene films was confirmed using surface measurements, including X-ray photoelectron spectroscopy, atomic force microscopy, and water contact angle goniometry. Significant inhibition of biofilm formation was achieved for both Gram-negative and Gram-positive bacteria.