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.
Highlights
The overuse of antibiotics has led to a worldwide rise in bacterial resistance over several decades with the specter of untreatable infections looming ever closer.[1−4] Some infections pose particular therapeutic difficulties, which have resulted in various antibiotics becoming ineffective
Modern wound dressings employ various polymeric biomaterials,[11,13,24−26] including hydrogels. The latter have the advantages of retaining moisture, exhibiting low cytotoxicity, cooling the wound to reduce pain, being highly absorbent, and, as we describe some may possess inherent antimicrobial activity.[26−29] Certain biomimetic polymers can mimic the chemical structure of mammalian cell membranes, which make them ideal candidates for in vivo biomedical applications where biocompatibility is of paramount importance.[16,19,26,30,31]
New control experiments conducted using biocompatible PMPC25-b-PHPMA275 diblock copolymer worm gels confirm that no antibacterial activity is observed in this case
Summary
The overuse of antibiotics has led to a worldwide rise in bacterial resistance over several decades with the specter of untreatable infections looming ever closer.[1−4] Some infections pose particular therapeutic difficulties, which have resulted in various antibiotics becoming ineffective. Treatment of low-grade or chronic wound infections has led to nonantibiotic treatments being sought Among these are the topical application of honey,[5−9] silver,[10−13] and cationic copolymers.[14−22] these approaches do not offer a panacea (e.g., silver may compromise wound healing and honey can be difficult to handle), so there is a clinical need to develop new therapies.[23] For this reason, biocompatible materials that are intrinsically antimicrobial and can be incorporated into dressings would be useful additions to the therapeutic arsenal for treating infected wounds. The latter have the advantages of retaining moisture, exhibiting low cytotoxicity, cooling the wound to reduce pain, being highly absorbent, and, as we describe some may possess inherent antimicrobial activity.[26−29] Certain biomimetic polymers can mimic the chemical structure of mammalian cell membranes, which make them ideal candidates for in vivo biomedical applications where biocompatibility is of paramount importance.[16,19,26,30,31]
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