In vivo drug releasing test of aIginate/chitOsan incorporated with vancomycin as a drug delivery system / 中国组织工程研究

ABSTRACT

BACKGROUND: An important development orientation of osteomyelitis treating is to prepare a drug delivery system which has the characteristics of excellent biocompatibility, degradable, lengthen drug-released time, source sufficient, as well as use security. Alginate and chitosan can be used as drug delivery system due to the superordlnary biological properties. OBJECTIVE: To explore the feasibility and safety of alginate/chitosan incorporated vancomycin (VCM/ACA) as release carrier, in addition, to compare the difference from systematic injection. DESIGN, TIME AND SETTING: An in vivo drug concentration determination, matching grouping experiment. The experiment was performed at the animal and orthopedics laboratories, Affiliated Zhongshan Hospital of Dalian University from August 2008 to March 2009. MATERIALS: The alginate solution and vancocin solution was uniform mixed followed by adding CaCO_3 and citrate sodium solution, then the mixed liquor was prepared for vancocin-calcium alginate gel beads with microcapsule preparation instrument. After that, the vancocin-calcium alginate gel beads were reacted with chitosan/vancocin mixed liquor and cellulose acetate to prepare for VCM/ACA release carrier. METHODS: Forty rabbits were prepared for middle of left femur bone defect models, and then randomized divided into 2 groups, with 20 animals in each group. In the local medication group, VCM/ACA release carrier was inlaid to the defects. In the systemic administration group, rabbits were intravenous injected 10% vancocin (10 mg/kg). MAIN OUTCOME MEASURES: The drug concentrations in the serum and bone tissues of the local medication group was detected by high performance liquid chromatograph at hours 0.5, 1, 6, 24, 72 and weeks 1, 2 after operation. In the systemic administration group, the drug concentrations in the serum, bone and muscle tissues were measured at minute 10 and hours 0.5, 1, 6, 24, and 72 after operation. In addition, histological sections of body tissues were prepared to look for signs of systemic toxicity of the implants. RESULTS: The serum drug concentrations of the systemic administration group were obvious greater than the local medication group at each time points prior to 24 hours, which less than the local medication group at hour 24. The drug concentration in bone and muscle tissues of local medication group were significant greater than the systemic administration group at different time points, which sustained for at least 2 weeks, while serum concentration in the systemic administration group was much lower than minimum inhibitory concentration after 24 hours. However, no multiple tissues revealed histological evidence of toxicity. CONCLUSION: There has feasibility and safety in vivo in course of ALM/VCM release carrier, which has superior effect to systemic administration.