Research On Design And Preparation Of Cationic Antimicrobial Polymer And Polymer-based Antimicrobial Carrier

Traditional antibiotics are powerful weapons to treat bacterial infections,but the overuse of antibiotics leads to antibiotic resistance of bacteria.At present,the antibiotic treatment methods being developed are not enough to cope with the growing threat of antibiotic resistance.Therefore,it is imperative to develop new antibacterial agents.This thesis mainly focuses on the design and preparation of polymer antibacterial agents and antibacterial carriers from three aspects,as well as the measurement and analysis of their antibacterial properties.Firstly,the main-chain sulfonium-containing polymer（Poly S⁺）was synthesized by mercaptan-epoxy"click"reaction and methylation reaction.By adjusting the feeding amount of methylation reagent,the methylation level of Poly S⁺can be reduced from 100%to 26%.The antibacterial activity of Poly S⁺can be increased by 2-16 times,but the cytotoxicity is only slightly increased.On the other hand,by studying the antibacterial test and biocompatibility test of Poly S⁺-34 with different batches and different molecular weight of 34%methylation level,it was found that the methylation level and biological activity were independent of batch differences and polymer chain length.Further theoretical research on antibacterial mechanism speculates that Poly S⁺can be used as an outer membrane penetrant to restore the antibacterial activity of antibiotics.The chessboard experiment showed that Poly S⁺-34 and rifampicin（Rif）had synergistic effect on E.coli.The biofilm removal experiment showed that when Poly S⁺-34/Rif reduced the bacteria in the 3-day mature biofilm by 8-log,the concentration of Poly S⁺-34decreased by 16 times compared with Poly S⁺-34 treated alone.To sum up,based on the controlled methylation reaction to balance the amphiphilic balance and charge density of the main chain matte salt,it can adjust its antibacterial efficacy,biocompatibility and the joint antibacterial between Poly S⁺polymer and antibiotic Rif.Methylation level of main chain matte salt is a reliable and practical means in the application of antibacterial control.Secondly,a series of quaternary ammonium salts P（TMAEMC-r-BMA）with different composition and structure were synthesized by using reversible addition-fracture chain transfer（RAFT）reaction and methylation reaction by adjusting the ratio of dimethylaminoethyl methacrylate（DMAEMA）and butyl methacrylate（BMA）.With the decrease of DMAEMA ratio,the antibacterial activity of P（TMAEMC-r-BMA）decreased,and the biological toxicity increased significantly,far greater than its antibacterial activity.Meanwhile,it is interesting that P(TMAEMC₆₀-r-BMA₄₀)and P(TMAEMC₄₀-r-BMA₆₀)and Rif together have achieved FICI values of 0.3125 and 0.375 for Escherichia coli,showing excellent synergistic effects.Thirdly,the azobenzene-norfloxacin coupling compound（Azo-Nor）was prepared by the reaction of acyl imidazole on azobenzene and secondary amine group on norfloxacin.Then,the hydrophilicα-Cyclodextrin oligomer（Oligoα-CD）and Azo-Nor to prepare hypoxia response azobenzene-nofloxacin/oligocyclodextrin carrier（Oligo-CD@Azo-Nor）.And it has been preliminarily proven to be feasible for the treatment of bacterial infections.Figure[68]table[8]reference[109]...