Preparation Of Amphiphilic Cationic Copolymers And Their Antibacterial Properties

Although the discovery and widespread use of antibiotics can effectively treat diseases caused by bacteria,antibiotics show poor therapeutic effects on treating chronic bacterial infections.Furthermore,the increasingly serious bacterial drug resistance has become an urgent global problem.Different from the antibacterial mechanism of antibiotics,amphiphilic cationic copolymers with the antimicrobial peptide-mimicing structure mainly act on the cell membrane of bacteria and play effect on a variety of antibiotic resistant bacteria.It is difficult for bacteria to develop resistance against the antibacterial mechanism of amphiphilic cationic copolymers.Therefore,with the advantages of broad-spectrum antimicrobial ability and easy realization for mass production,antibacterial cationic copolymers have become an important field for new antiseptics.In this dissertation,by using hydrophobic modified quaternary ammonium salts（MTAI）as the cationic segments,a series of diblock polymers m PEG-b-P（RMA_x-co-MTAI_y）（m PR_x/T_y）with different lengths of alkyl side chains were synthesized,and their antibacterial properties were studied.The results indicated that the antibacterial activity of the polymers（m PR_x/T_y）gradually increased and then decreased with the increase of the alkyl side chain length.When the alkyl side chain contained four carbon atoms,the highest selectivity between bacteria and red blood cells occurred on the polymer(m PB₃₅/T₅₇).The morphology of the bacteria that treaed with m PB₃₅/T₅₇ was observed by SEM and TEM.Combined with the results of PI staining assay,it was preliminarily speculated that m PB₃₅/T₅₇ could interact with the bacterial wall/membrane,destroy the structural integrity of the bacteria,cause the leakage of cytoplasmic matrix and eventually lead to the death of the bacteria.The 15-day resistance progress assay showed that E.coli and S.aureus are not easy to develop resistance to m PB₃₅/T₅₇.To explore the influence of the hydrophilic/hydrophobic balance on the antibiofilm activity of the cationic polymers,a series of diblock polymers m PEG-b-P（BMA_x-co-MTAI_y）（m PB_x/T_y）were synthesized by changing the molar ratio of BMA to MTAI.It was observed that m PB₃₅/T₅₇ showed higher antibacterial activity than the other two polymers(m PB₁₁/T₈₂ and m PB₇₇/T₁₁).The results proved that the hydrophilic/hydrophobic balance played an important role when the polymer act on the biofilm.Excessive positive charges or hydrophobic segments were not conducive to the interaction between the polymer and the biofilm.Finally,the pH sensitive monomer DPA was used to synthesize a series of triblock polymers m PEG-b-P（BMA-co-MTAI）-b-PDPA_x（m PB/T-D_x）,and the polymer nanomicelles were prepared.The results showed that although m PB/T-D₉₂ had lowest bactericidal activity,it showed similar antibiofilm ability to the other two polymers(m PB/T-D₅₂ and m PB/T-D₇₆)at the same concentration.That might prove that nanomicelles can eradication bacterial biofilms through mechanisms other than sterilization.