Investigating the Antimicrobial Potential of Metallic Based Nanoparticles and their Integration within Biocompatible Polymers

Abstract

Antimicrobial resistance of pathogenic infections is a rising global issue resulting in less effective antibiotic treatments against infections, thus leading to prolonged hospitalisation, higher mortality rates and increased healthcare costs. Therefore, the aim of this research is to extend the exploration of nanomaterials with antimicrobial activity and utilise them for the development of biomedical devices. In this endeavour, nanoparticles have been found to provide one possible alternative solution to tackle the challenges of antibiotic resistance. Metal nanoparticles, in particularly silver and copper, have shown promising antimicrobial potential for bioengineering and biomedical material applications. However, only a limited number of nanoparticles and their effects on common bacteria from hospital acquired infections (HAI) have been studied. This investigation extends knowledge of the antimicrobial activity of relevant nanoparticles. In this research, a variety of nanoparticles, including mono-metallic, bimetallic and graphene-based materials, were screened against common fungi, Gram-negative and Gram-positive bacteria that were listed by World Health Organisation (WHO) as a priority for the development of new antibiotics due to their multiple antibiotic resistances. Results demonstrated that these metallic based nanoparticles exhibited antimicrobial activity against a wide range of microbes, with elemental silver (Ag), bimetallic silver copper (AgCu) and elemental copper (Cu10) suspension nanoparticles displaying the broadest range of efficacies, with minimal inhibitory concentrations as low as 7.81 µg/ml. Upon the selection of antimicrobial nanoparticles, extended investigations on the antimicrobial activity were performed against E. coli, S. aureus and C. albicans. Based on the antimicrobial range and efficacy results, bimetallic AgCu nanoparticles were selected for further investigation. The properties of AgCu were explored and compared to Cu10 and Ag to help understand the link between the physio-chemical properties and the antimicrobial efficacy. It was found that hydrodynamic size and release of ions contributed the most to the antimicrobial effect of the nanoparticles. With this in mind, the mechanisms of action of the AgCu nanoparticles were investigated. Through observational techniques such as TEM and SEM, it was found that AgCu nanoparticles caused morphological changes to the microbes, including cell membrane damage, shrinkage in cell size by 10-35% and leakage of internal material. Furthermore, physical contact with C. albicans and S. aureus was observed. In bacterial cells, an increase of up 318% in oxidative stress and decrease in deoxyribonucleic acid (DNA) production to less than 13% was measured after incubation with AgCu nanoparticles. The selected nanoparticle, AgCu, was then fabricated into polymers with potential biomedical applications. Firstly, AgCu nanoparticles were incorporated into polydimethylsiloxane (PDMS) films. Films were produced with nanoparticles well dispersed throughout the film as observed via scanning electron microscopy (SEM); however no antimicrobial activity was exhibited. As a result, the films were surface treated with UV lamp, which resulted in an increase of AgCu nanoparticle exposure and ion release, leading to a 9.8% to 71.8% reduction in microbial growth (P = 0.05), depending on the microbial strain. A second application involved incorporating AgCu nanoparticle into polycaprolactone/polyethylene oxide (PCL/PEO) polymers. Through the disk diffusion method, it was found that the AgCu incorporated PCL/PEO films exhibited antimicrobial activity towards E. coli, S. aureus and C. albicans. The films had hydrophilic properties and partly dissolved upon contact with water. This resulted in the exposure and release of AgCu nanoparticles and ions thus leading to antimicrobial activity with zone of inhibition diameters between 1.04 cm to 4.20 cm, depending on microbial strain and AgCu nanoparticle concentration. Additionally, pores were found on the surface of the PCL/PEO polymers which has been suggested to provide benefits as wound dressing applications. However, the toxicity and biocompatibility of these AgCu nanoparticle incorporated PCL/PEO polymers requires investigation and validations with mammalian cells. These experiments have proven that certain nanoparticles provide antimicrobial activity against a wide spectrum of pathogenic species and can be incorporated in to polymers to fabricate antimicrobial films. However, further studies are required to fully elucidate the mechanism of action, the factors that can influence their antimicrobial effectiveness and toxicity as biomedical applications.