Combinatorial wound dressings loaded with synergistic antibiotics in the treatment of chronic infected wounds

Advanced medicated wound dressings fabricated by electrospinning and electrospraying were prepared for the eradication of topical bacterial infections potentially applied in the management of infected acute and chronic non-healing wounds. Two different antibiotics (ciprofloxacin and rifampicin), with different aqueous solubilities and different mechanisms of antimicrobial action, were loaded within electrosprayed polymer microparticles and within electrospun nanofibers, respectively, to provide the resulting wound dressing with dually controlled antibiotic release kinetics. Due to the large surface area per volume ratio of the electrosprayed microparticles containing ciprofloxacin, an initial burst release was obtained. Simultaneously, the reduced surface area per volume ratio for the electrospun nanofibers together with the reduced aqueous solubility of rifampicin produced an extended rifampicin release over time. More importantly, a synergistic antimicrobial effect against Gram-positive and Gram-negative bacteria was observed when both antibiotics were combined. Biofilm formation prevention and the elimination of already formed mature bacterial biofilms were also successfully achieved using our advanced dressings. The lack of cytotoxicity of the advanced wound dressings here reported against eukaryotic cells at antimicrobial doses was also demonstrated using three different mammalian cell lines. Moreover, the advanced wound dressings successfully eliminated a Staphylococcus aureus mediated experimental infection in a chronic wound murine model showing their efficacy for the treatment of these complicated non-healing wounds. The strategy of advanced medicated wound dressings developed here may be used as a potential methodology for the fabrication of functional combinatorial materials that offer the ability to eradicate bacterial infections

Elucidating the mechanisms of action of antibiotic-like ionic gold and biogenic gold nanoparticles against bacteria

The antimicrobial action of gold depends on different factors including its oxidation state in the intra- and extracellular medium, the redox potential, its ability to produce reactive oxygen species (ROS), the medium components, the properties of the targeted bacteria wall, its penetration in the bacterial cytosol, the cell membrane potential, and its interaction with intracellular components. We demonstrate that different gold species are able to induce bacterial wall damage as a result of their electrostatic interaction with the cell membrane, the promotion of ROS generation, and the consequent DNA damage. In-depth genomic and proteomic studies on Escherichia coli confirmed the superior toxicity of Au (III) vs Au (I) based on the different molecular mechanisms analyzed including oxidative stress, bacterial energetic metabolism, biosynthetic processes, and cell transport. At equivalent bactericidal doses of Au (III) and Au (I) eukaryotic cells were not as affected as bacteria did, maintaining unaffected cell viability, morphology, and focal adhesions; however, increased ROS generation and disruption in the mitochondrial membrane potential were also observed. Herein, we shed light on the antimicrobial mechanisms of ionic and biogenic gold nanoparticles against bacteria. Under selected conditions antibiotic-like ionic gold can exert a strong antimicrobial activity while being harmless to human cells