A Skeletal Drug Delivery System Of Nano-hydroxyapatite/Chitosan-Ciprofloxacin

ObjectiveWe designed this experiment to investigate the character of drug delivery kinetics of a new skeletal drug delivery system (DDS), nano- hydroxyapatite/ chitosan-ciprofloxacin, and its effect on the repair of local bone tissue by observing the release of ciprofloxacin in vitro and in vivo when implanted into tibia defect of rabbit.MethodCiprofloxacin was mixed with nano-hydroxyapatite/chitosan which acted as the vector, then the complex was made into drag delivery system. The DDS cylinders contained 10mg or 20mg ciprofloxacin separately. In vitro, the DDS cylinders were immersed in PBS, and the ciprofloxacin concentration in soak was measured after 1day, 3days and 1,2,4, 6, 8,10,12 weeks. In vivo, the DDS cylinders were implanted into the defects in left tibial tubercle of New Zealand rabbits. Rabbits were sacrificed 3 days, 1,2,4, 6, 8, 12 weeks after operation. Ciprofloxacin concentration in serum and tissue around the defect was measured. The repair of local tissue wasobserved by x-ray and pathological sections. HPLC was applied to the measurement of ciprofloxacin concentration.ResultsIn vitro, the release of ciprofloxacin began in one day, and its peak appeared during 4 and 6 weeks. Then the release decreased gradually but maintained at a high level relatively till 12 weeks later. And the release of cylinders contained 20mg ciprofloxacin is more than those contained lOmg ciprofloxacin. In vivo, ciprofloxacin in serum is extremely low or not detectable. Ciprofloxacin in bone tissue was detected 3 days after surgery, and the concentration increased gradually. 6 weeks later, the concentration reached the peak, 38.63±3.44mg/L. Then the release decreased. 12 weeks later, the concentration was 14.85 ± 3.94mg/L. The concentration of ciprofloxacin was always higher than the MIC of ciprofloxacin through our observation. From sections and x-ray, good repair of tissue around DDS was observed. New bone was found, much woven bone was found after 8 weeks, and lamellar bone appeared 12 weeks later.ConclusionNano-hydroxyapatite/chitosan is a promising vector of drug delivery system. Ciprofloxacin can release constantly at a high concentration in local tissue when it commixed with the complex. The DDS can fulfil the purpose of therapy and facilitate bone repair. Nano-hydroxyapatite/chitosan-ciprofl -oxacin has a good perspective as a DDS, and is remarkable to research more.