Nitric Oxide-Loaded Antimicrobial Polymer for the Synergistic Eradication of Bacterial Biofilm.

Bacterial biofilms are often difficult to treat and represent the main cause of chronic and recurrent infections. In this study, we report the synthesis of a novel antimicrobial/antibiofilm polymer that consists of biocompatible oligoethylene glycol, hydrophobic ethylhexyl, cationic primary amine, and nitric oxide (NO)-releasing functional groups. The NO-loaded polymer has dual-action capability as it can release NO which triggers the dispersion of biofilm, whereas the polymer can induce bacteria cell death via membrane wall disruption. By functionalizing the polymers with NO, we observed a synergistic effect in biofilm dispersal, planktonic and biofilm killing activities against Pseudomonas aeruginosa. The NO-loaded polymer results in 80% reduction in biofilm biomass and kills >99.999% of planktonic and biofilm P. aeruginosa cells within 1 h of treatment at a polymer concentration of 64 µg mL-1. To achieve this synergistic effect, it is imperative that the NO donors and antimicrobial polymer exist as a single chemical entity, instead of a cocktail physical mixture of two individual components. The excellent antimicrobial/antibiofilm activity of this dual-action polymer suggests the advantages of combination therapy in combating bacterial biofilms.

Poly(ethylene glycol)-Based Coatings Combining Low-Biofouling and Quorum-Sensing Inhibiting Properties to Reduce Bacterial Colonization.

Infections resulting from the formation of biofilms on medical devices remain a significant clinical problem. There is growing consensus that coatings displaying multiple defense mechanisms, such as low biofouling combined with surface active antimicrobial agents, is required. Quorum sensing (QS) is a bacterial mechanism used to coordinate their collective behavior. QS can also be exploited for antimicrobial purposes, to minimize colonization and biofilm formation by hindering bacterial communication. We have investigated a poly(ethylene glycol) (PEG) based multifunctional coating that allows the covalent incorporation of the synthetic QS inhibitor 5-methylene-1-(prop-2-enoyl)-4-(2-fluorophenyl)-dihydropyrrol-2-one (DHP) with a surface providing reduced cell attachment and bacterial adhesion. The simple coating, which can be applied using either a one- or two-step procedure, provides the first example for a multifunctional surface offering a combination of a quorum sensing inhibitor with a low biofouling background. X-ray photoelectron spectroscopy (XPS) was utilized to confirm the coating formation and the incorporation of DHP. L929 mouse fibroblast cell attachment and cytotoxicity studies demonstrated the low biofouling and biocompatible properties of the coatings. Bacterial colonization assays using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated the ability of these combination coatings to reduce the formation of biofilms. Importantly, the results demonstrate that the DHP remained active after covalent incorporation into the coating.

Antimicrobial peptide melimine coating for titanium and its in vivo antibacterial activity in rodent subcutaneous infection models.

Implant-associated infections represent a significant health problem and financial burden on healthcare systems. Current strategies for the treatment or prevention of such infections are still inadequate and new strategies are needed in this era of antibiotic resistance. Melimine, a synthetic antimicrobial peptide with broad spectrum activity against bacteria, fungi and protozoa, has been shown to be a promising candidate for development as antimicrobial coating for biomedical devices and implants. In this study, the in vitro and in vivo antimicrobial activity of melimine-coated titanium was tested. The titanium surface was amine-functionalised with 3-aminopropyltriethoxysilane (APTES) followed by reaction with a bifunctional linker 4-(N-maleimidomethyl)cyclohexane-1-carboxylic 3-sulfo-n-hydroxysuccinimide ester (Sulfo-SMCC) to yield a maleimide functionalised surface. Melimine was then tethered to the surface via a thioether linkage through a Michael addition reaction of the cysteine at its N-terminus with the maleimide moiety. Melimine coating significantly reduced in vitro adhesion and biofilm formation of Pseudomonas aeruginosa by up to 62% and Staphylococcus aureus by up to 84% on the titanium substrates compared to the blank (p < 0.05). The activity was maintained after ethylene oxide gas sterilisation. The coating was also challenged in both mouse and rat subcutaneous infection models and was able to reduce the bacterial load by up to 2 log10 compared to the uncoated surface (p < 0.05). Melimine coating is a promising candidate for development as a surface antimicrobial that can withstand industrial sterilisation while showing good biocompatibility.

Immobilization of antibacterial dihydropyrrol-2-ones on functional polymer supports to prevent bacterial infections in vivo.

Antibiotic-resistant Staphylococcus aureus is of great concern, as it causes a wide range of life-threatening infections. The current study demonstrates that dihydropyrrolone (DHP)-coated polyacrylamide substrates are effective in reducing the number of culturable clinical isolates of S. aureus in vitro in a dose-dependent manner and are able to reduce the pathogenic potential of staphylococcal infection in a subcutaneous infection model. Covalently bound DHPs therefore show great potential for use as an antimicrobial strategy in device-related applications.