Antibacterial Study On The Vancomycin-Loaded ZIF-8 With Hyaluronic Acid Modification

Nowadays,Methicillin-Resistant Staphylococcus Aureus?MRSA?has emerged as one of the greatest public health threats in the history of antibiotic chemotherapy.Scientific reports have proven that MRSA is a major cause of hospital-acquired infections not only include mild skin and soft tissue injury but also link to life-threatening endocarditis,chronic osteomyelitis and severe pneumonia.Even worse,these diseases are known to be associated with organ dysfunction,poor outcomes with excess morbidity and mortality,and high costs to the health care system,which are awaited to be treated urgently through a novel and efficient antimicrobial therapy.Vancomycin?Van?,a broad-spectrum glycopeptide antibiotic which is sensitive to Gram-positive bacteria,has been widely employed to prevent and treat staphylococcal isolates such as MRSA.However,large doses of intravenous administration of that may cause side effects such as ototoxicity and nephrotoxicity.Nanotechnology has significantly impacted the outcome of cancer treatments and is showing impressive potential in the management of bacterial infection.However,most reported nanomaterials are enormously toxic and also need a multistep synthetic process.In the face of these challenges,there is a growing need for a simpler,more effective method to synthesize safe antibacterial agents for combating MRSA.Here,we designed a targeted drug-loaded system that compounding hyaluronic acid with ZIF-8 through a simple and fast process.We hypothesized that HA were deposited to a zeolite-type metal-organic framework?ZIF-8?through the coordination of the carboxyl groups of HA and Zn²⁺?ZVH?.We performed scanning electron microscopy?SEM?,ultraviolet-visible absorption spectroscopy?UV-vis?,thermogravimetric analysis?TGA?,and nanometer particle size analyzer measurements on ZVH for structural characterizations,which proved the successful synthesis and structual stability of ZVH nanoparticles.The p H-triggered dynamic behavior was monitored to explore the p H responsiveness of ZVH for controlled release.The biosecurity of formulated ZVH was detected both in vitro and in vivo.The potential of ZVH as a promising drug-loaded nanosystem for chemotherapeutic treatment was verified by bacteriostasis test,competition inhibition test,intracellular bacteria clearance test,in vivo drug enrichment test and in vivo drug efficacy evaluation.Studies have shown that the modification of HA limits the agglomeration of dispersed nano-ZIF-8 particles and improves the water dispersion of nano-particles.The particle size of ZVH nanoparticles is 389nm,and the drug loading of Van is 33.73%.HA can specificall y bind to the highly expressed CD44 receptor on macrophages,thereby targeting bacterial infection sites and effectively killing pathogenic bacteria under acidic environment stimulat ion.Structural characterization proves that ZVH is successfully prepared and stable at room temperature,and the p H release curve proves that ZVH nanoparticles can be released by p H change,the drug release amount reached 60%within 24 h,and can be stable under physiological conditions,which is ZVH As the structural basis of the nano drug-loading system.ZVH can target antibiotics,controllable release,and give full play to the treatment of severely infected sites.In vivo and in vitro toxicity test results show that ZVH has good biocompatibility and very low biotoxicity.Cell phagocytosis experiments show that ZVH can enter the biological"barrier"cell membrane through HA-mediated endocytosis,to achieve drug enrichment and eradicate MRSA infections that are difficult to treat.The results of a model of treating pneumonia in mice by in vivo administration show that the nano drug-loading system has a better effect than traditional antibiotics alone,improves the traditional way of drug administration,and provides for further overcoming the resistance of bacteria to antibiotics and reducing the side effects of antibiotics possible.