ABSTRACT
There is currently an urgent need for the development of new antibacterial agents to combat the spread of antibiotic-resistant bacteria. We explored the synthesis and antibacterial activities of novel, sugar-functionalized phosphonium polymers. While these compounds exhibited antibacterial activity, we unexpectedly found that the control polymer poly(tris(hydroxypropyl)vinylbenzylphosphonium chloride) showed very high activity against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and very low haemolytic activity against red blood cells. These results challenge the conventional wisdom in the field that lipophilic alkyl substituents are required for high antibacterial activity and opens prospects for new classes of antibacterial polymers.
Subject(s)
Anti-Bacterial Agents/chemistry , Polymers/chemistry , Sugars/chemistry , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Hemolysis/drug effects , Hydrophobic and Hydrophilic Interactions , Microbial Sensitivity Tests , Organophosphorus Compounds/chemistry , Polymers/chemical synthesis , Polymers/pharmacology , Staphylococcus aureus/drug effects , Vinyl Compounds/chemistryABSTRACT
The ability to manipulate block copolymers on the nanoscale has led to many scientific and technological advances. These include nanoscale ordered bulk and thin films and also solution phase components; these are promising materials for making smaller ordered electronics, selective membranes, and also biomedical applications. The ability to manipulate block copolymer material architectures on such small scales has risen from thorough investigations into the properties that affect the architectures. Polyelectrolytes are an important class of polymers that are used to make amphiphilic block copolymers. In this context the authors synthesized polystyrene-b-polyphosphonium block copolymers with different anions coordinated to the polyphosphonium block in order to study the effect of the anion on the aqueous self-assembly of the polymers. The anions play an important role in the solubility of the monomeric materials which results in differences in the self-assembly observed through dynamic light scattering and transmission electron microscopy.
ABSTRACT
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.
