Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.

BackgroundBacterial cell quantification after exposure to antimicrobial compounds varies widely throughout industry and healthcare. Numerous methods are employed to quantify these antimicrobial effects. With increasing demand for new preventative methods for disease control, we aimed to compare and assess common analytical methods used to determine antimicrobial effects of novel nanoparticle combinations on two different pathogens.MethodsPlate counts of total viable cells, flow cytometry (LIVE/DEAD BacLight viability assay) and qPCR (viability qPCR) were used to assess the antimicrobial activity of engineered nanoparticle combinations (NPCs) on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria at different concentrations (0.05, 0.10 and 0.25 w/v%). Results were analysed using linear models to assess the effectiveness of different treatments.ResultsStrong antimicrobial effects of the three NPCs (AMNP0–2) on both pathogens could be quantified using the plate count method and flow cytometry. The plate count method showed a high log reduction (>8-log) for bacteria exposed to high NPC concentrations. We found similar antimicrobial results using the flow cytometry live/dead assay. Viability qPCR analysis of antimicrobial activity could not be quantified due to interference of NPCs with qPCR amplification.ConclusionFlow cytometry was determined to be the best method to measure antimicrobial activity of the novel NPCs due to high-throughput, rapid and quantifiable results.

A one step approach to prepare hybrid nanoparticle embedded polymer fibres using pressurised gyration is presented. Two types of novel antimicrobial nanoparticles and poly(methylmethacrylate) polymer were used in this work. X-ray diffraction analysis of the nanoparticles revealed Ag, Cu and W are the main elements present in them. The concentration of the polymer solution and the nanoparticle concentration had a significant influence on the fibre diameter, pore size and morphology. Fibres with a diameter in the range of 6-20μm were spun using 20wt% polymer solutions containing 0.1, 0.25 and 0.5 wt% nanoparticles under 0.3MPa working pressure and a rotational speed of 36,000rpm. Continuous, bead-free fibre morphologies were obtained for each case. The pore size in the fibres varied between 36 and 300nm. Successful incorporation of the nanoparticles in polymer fibres was confirmed by energy dispersive x-ray analysis. The fibres were also gyrospun on to metallic discs to prepare filters which were tested for their antibacterial activity on a suspension of Pseudomonas aeruginosa. Nanoparticle loaded fibres showed higher antibacterial efficacy than pure poly(methylmethacrylate) fibres.

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Antibiotic resistance is a major threat to public health, which contributes largely to increased mortality rates and costs in hospitals. The severity and widespread nature of antibiotic resistance result in limited treatments to effectively combat antibiotic-resistant pathogens. Nanoparticles have different or enhanced properties in contrast to their bulk material, including antimicrobial efficacy towards a broad range of microorganisms. Their beneficial properties can be utilised in various bioengineering technologies. Thus, antimicrobial nanoparticles may provide an alternative to challenge antibiotic resistance. Currently, nanoparticles have been incorporated into materials, such as fibres, glass and paints. However, more research is required to elucidate the mechanisms of action fully and to advance biomedical applications further. This paper reviews the antimicrobial efficacies and the intrinsic properties of different metallic nanoparticles, their potential mechanisms of action against certain types of harmful pathogens and how these properties may be utilised in biomedical and healthcare products with the aim to reduce cross contaminations, disease transmissions and usage of antibiotics.

The coupling reactions of polyethylene glycol (PEG) with two different nano-carbonaceous materials, graphene oxide (GO) and expanded graphene oxide (EGO), were achieved by amide bond formations. These reactions yielded PEGylated graphene oxides, GO-PEG and EGO-PEG. Whilst presence of the newly formed amide links (NH-CO) were confirmed by FTIR stretches observed at 1732 cm−1 and 1712 cm−1, the associated Raman D- and G-bands resonated at 1311/1318 cm−1 and 1584/1595 cm−1 had shown the carbonaceous structures in both PEGylated products remain unchanged. Whilst SEM images revealed the nano-sheet structures in all the GO derivatives (GO/EGO and GO-PEG/EGO-PEG), TEM images clearly showed the nano-structures of both GO-PEG and EGO-PEG had undergone significant morphological changes from their starting materials after the PEGylated processes. The successful PEGylations were also indicated by the change of pH values measured in the starting GO/EGO (pH 2.6–3.3) and the PEGylated GO-PEG/EGO-PEG (pH 6.6–6.9) products. Initial antifungal activities of selective metallic nanomaterials (ZnO and Cu) and the four GO derivatives were screened against Candida albicans using the in vitro cut-well method. Whilst the haemocytometer count indicated GO-PEG and copper nanoparticles (CuNPs) exhibited the best antifungal effects, the corresponding SEM images showed C. albicans had, respectively, undergone extensive shrinkage and porosity deformations. Synergistic antifungal effects all GO derivatives in various ratio of CuNPs combinations were determined by assessing C. albicans viabilities using broth dilution assays. The best synergistic effects were observed when a 30:70 ratio of GO/GO-PEG combined with CuNPs, where MIC50 185–225 μm/mL were recorded. Moreover, the decreased antifungal activities observed in EGO and EGO-PEG may be explained by their poor colloidal stability with increasing nanoparticle concentrations.

The complexes formed from the reaction of N-acylated tris-(pyridin-2-yl)methylamine (LH) with [Re(CO)(5)Br] depend on the structure of the ligand and the reaction conditions. Thus, while N-[1,1,1-tris-(pyridin-2-yl)methyl]acetamide coordinates through the three pyridine nitrogens to give a stable cationic complex [LHRe(CO)(3)Br], the analogous N-benzoyl ligand reacts under similar conditions to give a neutral complex [LRe(CO)(3)] with coordination through two pyridine nitrogens and a deprotonated amide. To try to explain these different outcomes, the reactions of some structurally related N-acylated [1,1-bis(pyridin-2-yl)]methylamines (L'H) with [Re(CO)(5)Br] have been studied and the reaction pathways identified. These studies indicate that a neutral complex [L'HRe(CO)(3)Br] is initially formed in which the amide portion of the ligand is uncoordinated, but that this complex under appropriate conditions then rearranges to give a cationic complex [L'HRe(CO)(3)]Br in which the coordinated amide nitrogen either remains protonated or is present in its imidic acid tautomeric form. Elimination of HBr from these complexes either thermally or in the presence of base then gives stable neutral complexes [L'Re(CO)(3)]. The impact of the N-acyl group and any substituent at the apex of the tripodal ligands (L''H) on the relative stabilities of intermediate complexes on the reaction pathway helps provide an explanation for the observed difference in behaviour of the N-acylated tris(pyridin-2-yl)methylamines (LH).

A convenient route to isoindolo[2,1-a]indol-6-ones has been developed starting from the appropriate 2-(N-phthaloyl)benzoic acids. Formation of the acid chlorides with thionyl chloride followed by heating with triethyl phosphite in a suitable solvent resulted in a multistep reaction giving tetracyclic β-ketophosphonates that on reduction with sodium borohydride gave the required indolones in good overall yields. Analogous β-ketophosphonates were also prepared starting with N,N-(1,8-naphthaloyl)-2-aminobenzoic acid and 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic acids although of these only the naphthaloyl product could be reduced with sodium borohydride without cleaving the amide bond in the ring system.