Research And Development Of A Novel Non-antibiotic Antimicrobial Agent-Gallium Compound

With the end of the "golden age" of antibiotics,human beings continue to face the challenge of bacterial resistance.Chitosan(CS),as a natural,safe and non-toxic antibacterial preservative,has wide application prospects in the fields of clothing,food and biomedicine.However,the antibacterial ability of chitosan itself is weak,and it is difficult to be used as a high-efficiency single antibacterial agent.Metal gallium ions can replace iron ions into bacteria like "Trojan horse".By blocking the iron metabolism process and interfering with the function of bacterial ferritin or iron-containing enzymes,the purpose of inhibiting bacterial growth and ultimately killing bacteria is achieved.Therefore,in this paper,gallium ions are used as exogenous antibacterial agents to prepare chitosan gallium complex(CS-Ga).The advantages of the CS-Ga complex are to improve the antibacterial efficiency,reduce the minimum inhibitory concentration(MIC),target the drug delivery of microbes,and overcome the resistance of bacteria through the synergistic antibacterial effect,The specific research content and results are as follows:(1)Using metal chelate method,using CS and GaCl3 as reactants,CS-Ga was successfully prepared,The viscosity-average molecular weight of CS-Ga determined by viscosity method was 1.712×104.Further,the synthesized chemical was characterized by using organic element analysis,inductively coupled plasma emission spectroscopy(ICP),infrared spectroscopy(FT-IR),X-ray crystal diffraction(XRD),thermal gravimetric analysis(TGA)and scanning electron microscopy(SEM).The results show that the content of gallium in CS-Ga is about 13.3%,and the ratio of chitosan monomer to gallium is 3:1.Compared with CS,CS-Ga shows significantly reduced particle size and thermal stability.(2)The minimum inhibitory concentration(MIC)of CS-Ga,the effect of different action time on the antibacterial performance of CS-Ga,and the effect of CS-Ga on the formation of bacterial biofilm were investigated through the in vivo antimicrobial test.The results show that at the same concentration,the antibacterial efficiencies of the product CS-Ga against both gram negative and positive bacteria are significantly improved compared to the reactants CS and GaCl3.The MIC of CS-Ga against E.coli and S.aureus were 0.18 mg/mL and 0.16 mg/mL,respectively.At the same concentration of gallium ion,the antibacterial efficiency of CS-Ga is increased more than 70%compared with GaCl3.Compared with CS only,the antibacterial efficiencies of CS-Ga against Gram-positive bacteria and Gram-negative bacteria are also improved.Especially for Gram-positive bacteria,at a lower concentration(0.10-0.15mg/mL),the antimicrobial efficacy of CS-Ga was increased by 40%.In addition,CS-Ga can quickly inhibit the growth of bacteria.It can inhibit 99%of S.aureus after only 60 minutes of mixed culture with the bacterial solution.Furthermore,CS-Ga has been shown a significant inhibitory effect on biofilm formation.Compared with CS and GaCl3 alone,CS-Ga has been showed more obvious inhibitory effect on bacterial activity and biofilm formation growth at the same drug concentration.(3)The CS-Ga/PVA nanofiber membrane was successfully prepared using a single-needle electrospinning device.The optimized conditions are 1.3%of the CS-Ga mass fraction,8%of the PVA mass fraction,20 kV of the spinning voltage,14 cm of the receiving distance,and 0.4 mL/h of the injection speed.With the stably spun of the spinning solution continuously,the fibers are smooth and relatively uniform.Further antibacterial experiments showed that the antibacterial activity of CS/PVA and CS-Ga/PVA composite nanofiber membranes against S.aureus was slightly higher than that of E.coli.Compared with the CS/PVA composite nanofiber membrane,the CS-Ga/PVA composite nanofiber membrane has higher MIC to E.coli and S.aureus,showing more excellent antibacterial properties.