Preparation Of Berberine Hydrochloride Inhalation And Study On The Treatment Of Respiratory Tract Staphylococcus Aureus Infection

Bacterial pneumonia is a pulmonary infection caused by bacteria invading the lower respiratory tract.It is the main cause of death in children all over the world.Staphylococcus aureus is the most common pathogen.Antibiotics are the main therapeutic drugs for bacterial pneumonia in the clinic.However,due to the long-term use of antibiotics,the drug resistance of bacteria continues to increase,and the efficacy of drug treatment continues to decline.Berberine hydrochloride has the strong broad-spectrum bacteriostatic effect,but its oral bioavailability is very low.Therefore,its application in the treatment of bacterial pneumonia is seriously limited.In the treatment of lung diseases,inhaled administration can directly deliver the drug to the lesion site,increase the drug concentration and avoid the first-pass effect of the liver.In this paper,berberine hydrochloride was made into a preparation that can be directly administered to the lungs.Then through inhalation administration,the drug acts directly on the infected site to increase its efficacy and effectively treat Staphylococcus aureus pneumonia.First,BH powder was prepared by spray drying and characterized by SEM,ACI and FT4.The results show that the lung deposition rate of the powder aerosol 76.4%,the aerodynamic diameter 4.61 μm,the stability index(SI)≈1 the inflation energy ratio(AR)=1.76>1,and the inflation energy(AE10)=2.1mJ<10mJ.Berberine hydrochloride powder aerosol has a high pulmonary deposition rate,good stability,low cohesion,low viscosity and good air permeability.Therefore,it can reach the depths of the lungs and meet the standard of inhalation preparations in the lungs.Subsequently,we established a bacterial pneumonia model with the help of Staphylococcus aureus.The aim is to verify the therapeutic effect of inhalable berberine hydrochloride powder.The number of leukocytes and neutrophils,the expression of inflammatory factors and lung histopathology were monitored in animal experiments.The results showed that inhaling berberine hydrochloride powder could effectively improve the pathological state of pneumonia rats and significantly reduce the expression of leukocytes,neutrophils and inflammatory factors(TNF-α,IL-1β and IL-6).Second,BH liposomes and penicillin liposomes were prepared in this study,Considering the advantages of liposomes for antimicrobial and pulmonary delivery.Their inhibitory effect on Staphylococcus aureus in vitro was investigated.The results showed that liposome preparation could reduce the MIC of Staphylococcus aureus by more than two times.Then,the biggest problem of bacterial infection is the removal of biofilm.Therefore,this study investigated the elimination effect of different berberine hydrochloride liposomes on Staphylococcus aureus biofilm.The results showed that berberine hydrochloride liposomes with high cholesterol had a better effect on the elimination of biofilm.Then the mechanism of berberine hydrochloride liposome against Staphylococcus aureus biofilm was studied.The results of SEM and TEM showed that the liposome with high cholesterol could remove the bacteria on the biofilm,interrupt the development and proliferation of the biofilm,destroy the spherical shape of the bacteria in the biofilm,dissolve the bacterial cell wall and decompose the bacteria into fragments.CLSM results showed that liposomes could significantly reduce the thickness of biofilm and the number of living bacteria.The results of the perforation test and fusion experiment showed that Staphylococcus aureus biofilm had a higher perforation rate and better fusion effect on liposomes with the high cholesterol content.In short,the liposome with a high cholesterol ratio can be better fused with the bacterial biofilm,releasing the drug into the biofilm and killing the bacteria inside.Finally,the tube with Staphylococcus aureus biofilm was implanted into the rat trachea to establish a model.The number of leukocytes,neutrophils,TNF-α,IL-1βand IL-6 was detected after administration.The pathological indexes of lung and the state of biofilm in endotracheal intubation were evaluated.The efficacy of berberine hydrochloride liposome inhalation in the treatment of respiratory tract biofilm infection was evaluated.The results showed that BH liposome could significantly remove the biofilm during endotracheal intubation,significantly reduce the expression of leukocytes,neutrophils and inflammatory factors in model rats,and significantly improve the pathological state of the lung in model rats.Therefore,it is concluded that aerosol inhalation of BH liposome can achieve the best effect in the treatment of respiratory tract biofilm infection.In this paper,BH powder and BH liposomes were prepared.They are used for inhalation to treat respiratory tract infections caused by Staphylococcus aureus.The pharmacodynamic effect and mechanism of BH liposomes with different cholesterol microdomains on Staphylococcus aureus biofilm were studied.The results showed that inhaled powder aerosol and liposome could improve the therapeutic effect of BH.The liposome is a kind of non-toxic and physiologically compatible vesicles,which can be used in the lung delivery system of anti-biofilm drugs to release the drugs into the biofilm and efficiently remove the biofilm.