Research On ZIF-8 Loaded Rifaximin For Anti-bacteria And Intervention Of Biofilm

Biofilms are special complexes formed by pathogens such as bacteria under certain adverse conditions.Unlike free pathogens,biofilms have a rich extracellular matrix and adhere closely to the surface of reusable medical devices and tissues.Traditional physical and chemical treatments such as antibiotics are difficult to effectively act on the cells themselves from the outside.In addition,it can lead to adverse medical consequences such as difficulty in wound healing and rejection of the implant.The Metal Organic Framework(MOFs)has excellent properties such as high porosity,wide catalytic properties and chemical stability.They are widely used in gas separation and reaction catalysis.In recent years,with the development of nanotechnology,MOF has gradually been used as a drug carrier for disease diagnosis and treatment.On this basis,this study aims to prepare drug-loaded ZIF-8 composite nanomaterials by various methods,and to explore the differences in morphology and properties of synthetic materials under different conditions.The ability of composite materials to kill planktonic bacteria under different p H conditions and remove bacterial biofilms was investigated.(1)We first start from the classic ZIF-8 synthesis route,change the synthesis conditions and use the one-pot method to successfully synthesize different morphologies(classical zeolite,cubic,and amorphous)and particle sizes(500 nm,200 nm,100 nm,50 nm,30 nm)ZIF-8 material.Secondly,starting from ZnO nanoparticles,ZIF-8 is synthesized based on ZnO,and ZIF-8@ZnO materials with different particle sizes(200 nm,60 nm)are prepared.Then combine the characteristics of the previous two methods to synthesize ZIF-8@Rifampicin(RFP),ZIF-8@Rifaximin(RFXM),ZIF-8@ZnO@Rifampicin(RFP)and ZIF-8@ZnO@Rifaximin(RFXM)composite nanomaterials.By measuring the loading rate,it is found that the drug loading rate of ZIF-8 nanoparticles synthesized based on ZnO is only 50% of that of the direct synthesis method.The materials synthesized by the two methods can successfully release the loaded drug at p H 6.0,and realize the controlled release of p H of the material.(2)Taking Staphylococcus aureus(SAU)as the object,the study material’s killing effect on planktonic bacteria.The results show that the materials synthesized by the two methods have better killing effects on SAU than the same concentration of Rifaximin(RFXM).It proves that ZIF-8 nanoparticles have a synergistic effect and enhance the bactericidal effect of the drug.In addition,the bactericidal effect of ZIF-8@ZnO@RFXM synthesized based on ZnO is better than that of ZIF-8@RFXM.Through XRD analysis,it is found that ZIF-8@ZnO@RFXM material contains ZnO.Combined with ICP-MS characterization,it is found that the release of zinc particles is also higher than that of ZIF-8@RFXM.We speculated that the presence of ZnO is responsible for the reason why ZIF-8@ZnO@RFXM has better sterilization performance.(3)Construct a SAU biofilm and use two materials for intervention.The amount of biofilm was measured by crystal violet staining method,and it was found that ZIF-8@ZnO@RFXM has stronger effect on reducing the amount of biofilm than ZIF-8@RFXM and RFXM alone.Combined with the staining of living and dead bacteria,it was observed by laser confocal microscope(CLSM)that ZIF-8@ZnO@RFXM loaded with 0.0293 μg/m L RFXM can effectively kill the bacteria in the biofilm.Finally,the cytotoxicity of the material was determined by the MTT method.The cell viability of 12.5 μg/m L ZIF-8@ZnO@RFXM(loaded with RFXM 1.5 μg/m L)was about 80% after 12 hours.In this study,we synthesize ZIF-8@ZnO@RFXM composite nanomaterials based on ZnO nanoparticles,and successfully used them for SAU planktonic bacteria killing and SAU biofilm removal.