Antimicrobial and antioxidant amphiphilic random copolymers to address medical device-centered infections

Microbial biofilms are known to support a number of human infections, including those related to medical devices. This work is focused on the development of novel dual-function amphiphilic random copolymers to be employed as coatings for medical devices. Particularly, copolymers were obtained by polymerization of an antimicrobial cationic monomer (bearing tertiary amine) and an antioxidant and antimicrobial hydrophobic monomer (containing hydroxytyrosol, HTy), To obtain copolymers with a various amphiphilic balance, different molar ratios of the two monomers were used. 1H-NMR and DSC analysis evidenced that HTy aromatic rings are able to interact each other leading to a supra-macromolecular re-arrangement and decreasing the copolymer size in water. All copolymers showed good antioxidant activity and Fe2+ chelating ability. Cytotoxicity and hemolytic tests evidenced that the amphiphilic balance, cationic charge density and polymer size in solution are key determinants for polymer biocompatibility. As for the antimicrobial properties, the lowest minimal inhibitory concentration (MIC=40 μg/mL) against S. epidermidis was shown by the water-soluble copolymer having the highest HTy molar content (0.3). This copolymer layered onto catheter surfaces was also able to prevent staphylococcal adhesion. The approach here reported permits not only to prevent biofilm infections but also to reduce the risk of emergence of drug-resistant bacteria. Indeed, the combination of two active compounds in the same polymer can provide a synergistic action against biofilm and suppress reactive species oxygen (ROS), known to promote the occurrence of antibiotic resistance.