Core-crosslinked amphiphilic block copolymer micelles for antibacterial applications

The aim of this study is to synthesize and characterize positively charged core crosslinked polymeric micelles for antibacterial applications. To achieve this aim, at first, the homopolymer of POEGMA (Poly (Oligo Ethylene Glycol Methyl Ether Methacrylate) was synthesized via RAFT polymerization (Reversible Addition-Fragmentation Chain Transfer Polymerization) and then it was used as a macro-RAFT agent to enable the synthesis of Poly (4-Vinyl pyridine) (PVP)-POEGMA block copolymer. When POEGMA-b-PVP amphiphilic copolymer was dissolved in water with bifunctional quaternization agent and heated, the copolymer self-assembled into core-crosslinked micelles. This study is first to report such core-crosslinked POEGMA-b-PVP copolymer-based micelles. The crosslinking and the quaternization agent 1, 6-Dibromohexane was used to quaternize PVP segment of the micelles. To investigate the effect of quaternization degrees on the antibacterial characteristics of the micelles, different amounts of 1, 6-Dibromohexane were used. Moreover, to clarify the effect of POEGMA on the antibacterial properties of the samples, quaternized PVP nanoparticle and POEGMA-b-PVP copolymer were also prepared and characterized. Gel Permeation Chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (Zeta Sizer), Scanning Electron Microscopy (SEM), Nuclear Magnetic Resonance Spectroscopy (NMR) and antibacterial assays were performed to characterize the obtained materials. The results revealed that POEGMA-b-PVP block copolymer was successfully synthesized by RAFT method in a controlled manner. The prepared core crosslinked micelles have an average particle size of 100 nm and zeta potential values within the range of (+25) - (+45) mV. To determine the antibacterial activity of the micelles, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were chosen as model microorganisms and three different methods were used namely, broth microdilution, disc diffusion and, agar diffusion. These micelles exhibited antibacterial activity against E. coli better than S. aureus after overnight incubation. Based on our findings, it can be concluded that the obtained positively charged core-crosslinked micelles can be used for antibacterial applications. Keywords: Micelles, Antibacterial, Block copolymer, RAFT Polymerization, Quaternization