Phosphonium-Functionalized Polymer Micelles with Intrinsic Antibacterial Activity.
New approaches to treat bacterial infections are badly needed to address the increasing problem of antibiotic resistance. This study explores phosphonium-functionalized block copolymer micelles as intrinsically antibacterial polymer assemblies. Phosphonium cations with varying alkyl lengths were conjugated to the terminus of a poly(ethylene oxide)-polycaprolactone block copolymer, and the phosphonium-functionalized block copolymers were self-assembled to form micelles in aqueous solution. The size, morphology, and ζ-potential of the assemblies were studied, and their abilities to kill Escherichia coli and Staphylococcus aureus were evaluated. It was found that the minimum bactericidal concentration depended on the phosphonium alkyl chain length, and different trends were observed for Gram-negative and Gram-positive bacteria. The most active assemblies exhibited no hemolysis of red blood cells above the bactericidal concentrations, indicating that they can selectively disrupt the membranes of bacteria. Furthermore, it was possible to encapsulate and release the antibiotic tetracycline using the assemblies, providing a potential multimechanistic approach to bacterial killing.
Department of Chemistry and Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario , 1151 Richmond Street, London, Canada N6A 5B7.
Benjamin
B
Hisey
Department of Chemistry and Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario , 1151 Richmond Street, London, Canada N6A 5B7.
Paul J
PJ
Ragogna
Department of Chemistry and Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario , 1151 Richmond Street, London, Canada N6A 5B7.|Department of Chemical and Biochemical Engineering, The University of Western Ontario , 1151 Richmond Street, London, Canada N6A 5B9.
Elizabeth R
0000-0002-3983-2248
ER
Gillies
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis; D008823:Micelles; D008826:Microbial Sensitivity Tests; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012756:Sheep; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D008823:Micelles; D009943:Organophosphorus Compounds; D011091:Polyesters; D011108:Polymers; C458722:polyethylene oxide-polycaprolactone copolymer; D011092:Polyethylene Glycols