Preparation Of Svnergistic Response Nano-carriers And Study On Antibacterial And Anti-inflammation

Inflammation is mainly a defense response of the body's immune system against external stimuli.Usually,inflammation is beneficial,but if left unchecked and leads to an excessive inflammatory response,which will cause more serious harm to the body,such as sepsis.In recent years,the rapid development of nanotechnology has led to extensive research and discussion in the field of drug delivery in biomedicine.How to use nanomaterials to deliver drugs through active targeting,high permeability and retention effects has become a new direction to combat infectious inflammation.In this thesis,multimodal synergistic drug delivery nanocarriers were prepared,and various therapeutic agents were loaded to combat the unfavorable factors in inflammation.The details are as follows:(1)Prussian blue nanocrystal(PBNC)of uniform size were synthesized with polyvinylpyrrolidone(PVP)as a reducing agent,and then hollow-structure Prussian blue nanocrystal(HPBNC)were prepared by controlled chemical etching in acidic conditions.The transmission electron microscope was used to verify the morphology and size of PBNC and HPBNC,and confirmed that HPBNC has a unique cavity structure.The crystal structure and chemical composition of the two crystals were tested by X-ray diffractometer and fourier transform infrared spectroscopy.The results proved that chemical etching will not affect the original properties of HPBNC.Afterward,the simulated enzyme activity of Prussian blue nanocrystal was studied,and it was found that PBNC and HPBNC have excellent peroxidase-like(POD)and catalase-like(CAT)activities,confirming their ability to eliminate ROS.(2)Poly(lactic acid-glycolic acid)copolymer(PLGA)nanoparticles loaded with the antibiotic sflufloxacin(SFX)and the anti-inflammatory drug tacrolimus(TAC)were prepared by the emulsion solvent evaporation method.Moreover,the y3 peptide,which can specifically bind to the inflammatory endothelial intercellular cell adhesion molecule(ICAM-1),was cross-linked to the surface of PLGA nanoparticles by glutaraldehyde.The transmission electron microscope,scanning electron microscope,dynamic light scattering,and high performance liquid chromatography were used to evaluate the morphology,size,surface properties,drug loading and drug release capabilities of the prepared drug carrier.The results showed that the y3-PLGA drug loading system has excellent physical properties,and in terms of loading and releasing properties were also met the experimental expectations.Through in vitro bacterial experiments and cell experiments,y3-PLGA has excellent antibacterial properties against both Gram-negative and Gram-positive bacteria,and has great targeting ability in inflammatory cells.(3)Through biocompatibility related experiments,it has been proven that?3-PLGA has lower cytotoxicity,hemolytic rate and immune response.A mouse model of acute bacterial pneumonia infection was established,and the in vivo imaging system(IVIS)was used to verify that fluorescently labeled y3-PLGA has targeting ability in infected tissues in vivo.Then,y3-PLGA co-loaded with SFX and TAC was administered to a mouse model of pneumonia,which could effectively reduce the inflammation and immune response of mice with acute lung infection and improve the survival rate of mice.