title: Antimicrobial Graft Copolymer Gels.
abstract: In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and 2-hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition-fragmentation chain transfer polymerization and characterized via (1)H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well-known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC-PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactant-like activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane.
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield , Brook Hill, Sheffield, South Yorkshire, S3 7HF, United Kingdom.|Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield , Claremont Crescent, Sheffield, South Yorkshire, S10 2TA, United Kingdom.|The Kroto Research Institute, Department of Engineering Materials, University of Sheffield , Broad Lane, Sheffield, South Yorkshire, S3 7HQ, United Kingdom.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Harvey
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield , Brook Hill, Sheffield, South Yorkshire, S3 7HF, United Kingdom.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield , Claremont Crescent, Sheffield, South Yorkshire, S10 2TA, United Kingdom.
authors.forename: C W Ian
authors.initials: CW
authors.lastname: Douglas
authors.affiliation: The Kroto Research Institute, Department of Engineering Materials, University of Sheffield , Broad Lane, Sheffield, South Yorkshire, S3 7HQ, United Kingdom.
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield , Brook Hill, Sheffield, South Yorkshire, S3 7HF, United Kingdom.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry*; D005782:Gels / Q000737:chemistry / Q000494:pharmacology*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D012212:Rheology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013499:Surface Properties
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D005782:Gels; D011108:Polymers