Preparation Of Magnetic Field Compliance Vancomycin Microspheres And Targeted Delivery In Bone Infection Therapy

Background:Fractures are frequently accompanied by soft tissue injury in recent years because open trauma and high-energy trauma increase.Treatment of fracture is not timely and wrong fixation could cause bone infection.The incidence of bone infection is gradually rising in recent years.Using large doses of sensitive antibiotics early is basis of treating bone infection.Topical application of antibiotics has its own unique advantages,and is accepted gradually by clinical workers.Although topical application of antibiotics for the treatment of bone infection is more attended,it has not been widely applied in clinical, because the existing methods have strong side effects,low effect and bad bone targeting. With the development of nanotechnology,there has been a new magnetism drug-carried system mediated by nanovector.In the magnetic field,the system can implement site-specific targeting drug administertion,which can raise drug concentration in the focus of infection,elevate therapeutic effect,and decrease side effect all over the body.The new magnetism drug-loading system has the controllable characteristic in vitro.We wish the idea can provide a new direction of bone infection therapy.Objective:1.Research the technique for magnetic field compliance vancomycin microspheres and to evaluate the characteristics of the prepared nanoparticles.2.Investigate anti-staphylococcus aureus effect of magnetic field compliance vancomycin microspheres in vivo.3.Establish the rat model of acute staphylococcal osteomyelitis.4.Investigate antibacterial effect of magnetic field compliance vancomycin microspheres in the rat model of acute staphylococcal osteomyelitis.Method:1.Take chitosan(CTS)as the vector of vancomycin.The magnetic field compliance vancomycin microspheres were prepared by emulsion-chemical crosslink.We observe the shape of nanoparticles by scanning electron microscope(SEM) and transmission electronmicroscope(TEM),determine the magnetism by vibrating samplemagnetometer (VSM) and evaluate the mean diameter,encapsulation ratio,drug loading,and so on.2.To verify antibacterial effect of magnetic field compliance vancomycin microspheres in vivo,the staphylococcus aureus(SA) were cultured in Petri dish,which contained magnetic field compliance vancomycin microspheres. 3.The staphylococcus aureus was inoculated directly into tibial bone of rat,and We assessed the relationship between inoculation dose and histological,radiological,and microbiological changes in the acute phase(1 week after inoculation) using this rat osteomyelitis model.4.To research therapeutic efficacy of the magnetic field compliance vancomycin microspheres to bone infection by observating the histological,radiological,and microbiological changes in the acute phase of rat model.Result:1.The magnetic field compliance vancomycin microspheres have been prepared succeed.The microspheres had regular spherical surfaces,the eighty percent of microsphereswere found to have the mean diameter within the range of 100-350nm,the drug loading was 32.36%,the mean encapsulation ratio was 80.9%,and had a good magnetic response in vitro.2.The staphylococcus aureus(SA) were cultured in Petri dish for 48 hours,which contained the magnetic field compliance vancomycin microspheres.The microspheres could effectively inhibit the growth of SA in vivo.the staphylococcus aureus(SA) were cultured in Petri dish for 48 hours,which contained the magnetic field compliance microspheres without vancomycin.The microspheres without vancomycin could not inhibit the growth of SA in vivo.The results showed that the magnetic field compliance vancomycin microspheres,could effectively inhibit the growth of SA in vivo.3.Development of significant histological and radiological signs of osteomyelitis required an inoculum of at least 6.0×10~2CFU/5μl staphylococcus aureus.The rat model demonstrated clear infective destruction in the tibia at a dose of 6.0×10~4CFU/5μl,with special reference to the acute stage only(1 week after infection).The rat model of acute staphylococcal osteomyelitis was established successfully.4.The application of the magnetic field compliance vancomycin microspheres in the treatment of bone infection was better,The actual vancomycin amount dosage of the magnetic field compliance vancomycin microspheres group was 1/3 of general usage group.There was no significant difference of the magnetic field compliance vancomycin microspheres group vs general usage group.Conclusions:1.The magnetic field compliance vancomycin microspheres have been prepared succeed.The method for preparing the magnetic field compliance vancomycin microspheres is simple and can meet the requirement of pharmaceutics,The microspheres had a good magnetic response.2.The magnetic field compliance vancomycin microspheres could effectively inhibit the growth of staphylococcus aureus in vivo.3.To established successfully the rat model of acute staphylococcal osteomyelitis,the staphylococcus aureus of at least 6.0×10~4CFU/5μl was inoculated directly into tibial bone of rat.4.In the field of magnetic,the magnetic field compliance vancomycin microspheres have satisfactory magnetic responsibility in vivo and in vitro,could obviously elevate drug concentration in targeting intraorganic,reinforce vancomycin effect,and relieve or avoid side effect.It is a dependable targeting preparation.