The antimicrobial efficacy of copper, cobalt, zinc and silver nanoparticles: alone and in combination.

With the advent of nanotechnology, there has been an extensive interest in the antimicrobial potential of metals. The rapid and widespread development of antimicrobial-resistant and multidrug-resistant bacteria has prompted recent research into developing novel or alternative antimicrobial agents. In this study, the antimicrobial efficacy of metallic copper, cobalt, silver and zinc nanoparticles was assessed againstEscherichia coli(NCTC 10538),S. aureus(ATCC 6538) along with three clinical isolates ofStaphylococcus epidermidis(A37, A57 and A91) and three clinical isolates ofE. coli(Strains 1, 2 and 3) recovered from bone marrow transplant patients and patients with cystitis respectively. Antimicrobial sensitivity assays, including agar diffusion and broth macro-dilution to determine minimum inhibitory and bactericidal concentrations (MIC/MBC) and time-kill/synergy assays, were used to assess the antimicrobial efficacy of the agents. The panel of test microorganisms, including antibiotic-resistant strains, demonstrated a broad range of sensitivity to the metals investigated. MICs of the type culture strains were in the range of 0.625-5.0 mg ml-1. While copper and cobalt exhibited no difference in sensitivity between Gram-positive and Gram-negative microorganisms, silver and zinc showed strain specificity. A significant decrease (p< 0.001) in the bacterial density ofE. coliandS. aureuswas demonstrated by silver, copper and zinc in as little as two hours. Furthermore, combining metal nanoparticles reduced the time required to achieve a complete kill.

Synergistic Antimicrobial Metal Oxide-Doped Phosphate Glasses; a Potential Strategy to Reduce Antimicrobial Resistance and Host Cell Toxicity.

The emergence of antimicrobial resistant strains bacteria and a decline in the discovery of new antibiotics has led to the idea of combining various antimicrobials to treat resistant strains and/or polymicrobial infections. Metal oxide-doped glasses have been extensively investigated for their antimicrobial potential; however to date, most experiments have focused on single metal species in isolation. The present study investigates the antimicrobial potential of sodium calcium phosphates (P2O5)50(Na2O)20(CaO)30-X(MO)X, where M is cobalt, copper, or zinc as single species. In addition, this work studied the effect of co-doping glasses containing two different metal ions (Co + Cu, Co + Zn, and Cu + Zn). The antimicrobial efficacy of all glasses was tested against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains, as well as a fungal strain (Candida albicans). Minimum inhibitory and bactericidal concentrations and time kill/synergy assays were used to assess the antimicrobial activity. An enhanced antimicrobial effect, at 5 mg/mL concentration, was exhibited by cobalt, copper, and zinc oxide glasses alone and in combinations. A synergistic antimicrobial effect was observed by Cu + Co and Cu + Zn against E. coli and Cu + Zn against S. aureus.

Antibacterial silver-doped phosphate-based glasses prepared by coacervation.

Phosphate-based glasses are materials of great interest for the regeneration and repair of damaged hard or soft tissues. They have the desirable property of slowly dissolving in the physiological environment, eventually being totally replaced by regenerated tissue. Being bioresorbable, they can simultaneously induce tissue regeneration and deliver therapeutic agents (e.g. antibacterial ions) in a controlled way. In this work, we have synthesised a series of glasses in the P2O5-CaO-Na2O system doped with Ag2O using the coacervation method. The addition of silver is known to provide the glass with antibacterial properties due to the release of Ag+ ions into the body fluid. The coacervation method is a facile, water-based technique which offers significant advantages over the conventional melt-quench route for preparing phosphate-based glasses which requires melting of metal oxide powders at high temperatures (1000-1200 °C). The properties of the initial colloidal polyphosphate systems (coacervates) as a function of the Ag2O content were characterised using rheology and liquid state 31P NMR. The effect of Ag+ addition on the final dried glasses was investigated using thermal analysis, Raman spectroscopy and X-ray diffraction. The antibacterial activity was assessed against Staphylococcus aureus (S. aureus), a bacterial strain commonly found in post-surgery infections. A dose-dependent antimicrobial effect was seen with an increasing silver content.

The antimicrobial efficacy of zinc doped phosphate-based glass for treating catheter associated urinary tract infections.

In this study, a series of phosphate-based glasses; (P2O5)50(Na2O)20(CaO)30-x (ZnO)x were prepared with increasing concentration of zinc oxide to determine the antimicrobial effect against clinically relevant microorganisms. The addition of 1 and 3 mol% zinc oxide decreased glass degradation however a higher dissolution rate was observed for 5 and 10 mol% ZnO. The antimicrobial results showed a concentration dependent effect on the viability of microorganisms. When in direct contact zinc doped glasses showed a complete kill, within 24 h, against Escherichia coli and a significant (p < 0.01) kill was observed against Staphylococcus aureus however the effect of dissolution products was not seen until 48 h. Furthermore, the cytotoxic studies showed no toxic effects on the viability of uroepithelial cells. This study has shown that zinc doped phosphate-based glasses can potentially be used to prevent/treat catheter associated urinary tract infections.

The Antimicrobial Efficacy of Hypoxia Mimicking Cobalt Oxide Doped Phosphate-Based Glasses against Clinically Relevant Gram Positive, Gram Negative Bacteria and a Fungal Strain.

Bioactive phosphate glasses are of considerable interest for a range of soft and hard tissue engineering applications. The glasses are degradable and can release biologically important ions in a controlled manner. The glasses can also potentially be used as an antimicrobial delivery system. In the given study, novel cobalt-doped phosphate-based glasses, (P2O5)50(Na2O)20(CaO)30-x(CoO)x where 0 ≤ x (mol %) ≤ 10, were manufactured and characterized. As the cobalt oxide concentration increased, the rate of dissolution was observed to decrease. The antimicrobial potential of the glasses was studied using direct and indirect contact methods against both Escherichia coli (NCTC 10538) Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 76615). The results showed strong, time dependent, and strain specific antimicrobial activity of the glasses against microorganisms when in direct contact. Antimicrobial activity (R) ≥ 2 was observed within 2 h against Escherichia coli, whereas a similar effect was achieved in 6 h against Staphylococcus aureus and Candida albicans. However, when in indirect contact, the dissolution products from the bioactive glasses failed to show an antimicrobial effect. Following direct exposure to the glasses for 7 days, osteoblast-like SAOS-2 cells showed a 5-fold increase in VEGF mRNA while THP-1 monocytic cells showed a 4-fold increase in VEGF mRNA expression when exposed to 10% CoO-doped glass compared with the cobalt free control glass. Endothelial cells stimulated with conditioned medium taken from cell cultures of THP-1 monocytes exposed to 10% CoO doped glass showed clear tubelike structure (blood vessel) formation after 4 h.

Development and Characterization of Gallium-Doped Bioactive Glasses for Potential Bone Cancer Applications.

In this study, we have developed a series of novel gallium oxide doped bioactive glasses to specifically target osteosarcoma cells while aiding new bone formation. The results show that osteosarcoma (Saos-2) cell death is induced through the addition of gallium oxide. Relative to the gallium-free control glass (0% Ga) glasses containing 1, 2, and 3% Ga decreased Saos-2 cell viability in a dose dependent manner. After 72 h in media preconditioned with 3% Ga Saos-2 cell viability was reduced by over 50%. Corresponding studies undertaken on primary normal human osteoblast cells (NHOst) demonstrated no adverse effects to the gallium containing glasses. Hydroxyapatite formation was observed for all glasses when exposed to simulated body fluid.