Studies On The Structure And Antibacterial Properties Of Amphiphilic Cationic Polymers

The major diseases caused by pathogenic microorganisms such as bacteria and the resistance of various pathogenic bacteria to antibiotics,pose a serious threat to human health.It is urgent to develop new high-efficiency antibacterial agents.As a kind of macromolecular antibacterial agent,cationic polymers have attracted wide attention due to its advantages including simple preparation,low cost and strong antibacterial properties,etc.In the previous studies on cationic polymers for gene carriers,our group had prepared a series of amphiphilic cationic polymers with poly(trimethylammonium methacrylate)and pH-sensitive hydrophobic segments,polyethylene glycol-poly(diisopropylamino-ethyl methacrylate/dimethylamino-ethyl methacrylate)-poly(trimethylammonium methacrylate)tri-block copolymer(mPEG-P(DPA/DMA)_X/Y-PTDMA)(TDDEs).On this basis,this paper studies the antibacterial properties of TDDEs.It was found that TDDEs exhibited high antibacterial ability,and the DPA/DMA composition of the polymer had a great influence on its antibacterial properties.When mole ratio of DPA/DMA was among 0.2?1,TDDEs showed the highest antibacterial effect both against E.coli and S.aureus.The antibacterial mechanism of TDDEs was analyzed by scanning electron microscopy,transmission electron microscopy,micro-spectrophotometry and fluorescent staining.It was preliminarily speculated that the antibacterial mechanism of TDDE-3 could be attributed to the cell membrane destory of the bacteria by TDDE-3 which caused the outflow of substances inside the bacteria.In order to explore whether the pH sensitivity of the hydrophobic segments in TDDEs is beneficial to its antibacterial effect,we replaced the pH-sensitive hydrophobic unit DPA in TDDEs with pH-insensitive n-butyl methacrylate(nBMA)to synthesize tri-block polymer mPEG-P(nBMA/DMA)-PTDMA(TDBE).The structure of the polymer was confirmed by ^IHNMR.The results of antibacterial experiments showed that there was no significant difference in the antibacterial properties between TDDEs and TDBE against E.coli and S.aureus,which indicated that the pH sensitivity of the hydrophobic segment in the polymer contributes little to the antibacterial properties.Therefore,continue to optimize the TDBE structure,the DMA in the P(nBMA/DMA)block on TDBE was removed,and the monomer ratio of nBMA/TDMA was kept unchanged.The simpler tri-block polymer mPEG-PnBMA-PTDMA(m PBT)and the diblock polymer mPEG-P(nBMA/TDMA)(m P(B/T))were synthesized.^IHNMR was used to confirm the successful preparation of the polymer.A comparative study on the antibacterial properties of TDBE,m PBT and m P(B/T)showed that the polymer m P(B/T)with nBMA/TDMA random copolymerization unit could kill nearly all the E.coli and S.aureus at a lower concentration.Next,in order to further improve the antibacterial properties of m P(B/T),the structural factors affecting its antibacterial properties were explored,including mPEG,nBMA/TDMA molar ratio and polymer molecular weight.Antibacterial experiments,hemolysis experiments and cytotoxic experiments have proved that the presence of mPEG in the polymer not only reduced hemolytic and cytotoxicity,but also enhanced the antibacterial activity;the antibacterial property of m P(B/T)has a large dependence on the nBMA/TDMA molar ratio and P(nBMA/TDMA)length,and m P(B/T)_35/57 has the best antibacterial activity,but its biocompatibility needs to be improved.