Main-Chain Cationic Poly(β-quaternary ammonium esters) (PBQAEs) as Potent Antibacterial Agents against Drug-Resistant Gram-Positive Bacteria

Abstract In this report, a systematic study on the antibacterial activity of poly(β-quaternary ammonium esters) (PBQAEs), a unique class of cationic polymers, is presented. The effects of main-chain ammonium groups and the chemical structures of side chains (e.g., hydrophilic ethylene glycols and hydrophobic alkyl chains) on the antibacterial performance are systematically examined. The results show that the polymer with a long alkyl side chain (P5Q) is a potent antibacterial agent with low MIC values against various Gram (+) bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA). The interaction of P5Q with the bacterial cells has been evaluated by a membrane depolarization assay to elucidate the mechanism of antibacterial action. The results indicate that P5Q interacts with and subsequently disrupts bacterial cell membranes by hydrophobic and electrostatic interactions, resulting in instant cell death. The in vitro cytotoxicity of P5Q against MCF-7 human breast cancer and HUVEC normal human umbilical vein endothelial cells is further evaluated by MTT assay. P5Q shows almost no acute mammalian cell toxicity in the concentration range between 2.0 and 32.0 μg/mL. To demonstrate the practical applicability of P5Q, polylactic acid (PLA) based electrospun nanofibers doped with P5Q have been successfully fabricated via electrospinning. The resulting composite fibers exhibit potent antibacterial activity, as characterized and validated by the disk diffusion assay.