左氧氟沙星聚乳酸-羟基乙酸共聚物纳米微球的制备及性能分析.

BACKGROUND: Conventional formulation of levofloxacin is rapidly and completely metabolized after administration. Fortunately, nanoparticle provides a new way to solve this problem. OBJECTIVE: To prepare a levofloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticle that can reduce administration frequency, maintain a stable and effective plasma concentration, and also can be combined with tissue-engineered scaffold materials. METHODS: Levofloxacin-loaded PLGA nanoparticles were prepared by emulsion solvent evaporation method. Twenty-four rabbits were taken to investigate the effect of nanoparticle formulation on the pharmacokinetics of levofloxacin and randomized into three groups (n=8 per group): general formulation group received an injection of levofloxacin (20 mg/kg) via ear vein; non-loaded nanoparticle group received an injection of blank nanoparticles; and levofloxaxin-loaded nanoparticle group received an injection of the corresponding levofloxacin-loaded nanoparticles. At different times, blood samples were collected to analyze the drug concentration of levofloxaxin. The antimicrobial activity of the levofloxacin-loaded nanoparticle was evaluated based on the rabbit model of Escherichia coli-induced urinary tract infection. Forty-five New Zealand white rabbits were used to establish urinary tract infection models and randomly divided into three groups (n=15 per group). In negative control group, rabbits received only an injection of normal saline via ear vein. In conventional formulation group, rabbits received an injection of levofloxacin (20 mg/kg). In nanoparticle group, rabbits received an injection of the corresponding levofloxacin nanoparticles. Subsequently, blood samples were obtained, and white blood cell (WBC) count and neutrophil percentage was tested; at the same time, the middle segment morning urine was collected to detect bacteriuria and urine WBC positive rates. At 9 days, the histopathologic analysis of the bladder mucosa was done. RESULTS AND CONCLUSION: (1) In vivo the pharmacokinetics: Compared with the conventional formulation group, the ideal levofloxacin-loaded PLGA nanoparticles prepared under optimal conditions significantly reduced the fluctuations in plasma concentration and frequency of administration. (2) Antimicrobial activity: Escherichia coli-induced urinary tract infection was gradually in control in the conventional formulation group and levofloxacin-loaded PLGA nanoparticle group, and basically cured at 9 days after injection. In addition, the number of cured patients was basically higher in the levofloxacin-loaded PLGA nanoparticle group than the conventional formulation group at the same time point, but there was a significant difference between the two groups only at 5 days after treatment. It can be concluded that levofloxacin-PLGA nanoparticles provide a well-sustained delivery system for treatment or prevention of urinary tract infections and provide a foundation for further investigations on tissue-engineered urethral reconstruction. [ABSTRACT FROM AUTHOR]