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| ZHAO Chen,WANG Qian,SHI Jiandang.Drug-releasing properties of anti-tuberculosis drugs composite in coating material HRZ/PLGA: a study in rats[J].Chinese Journal of Spine and Spinal Cord,2016,(7):635-641. |
| Drug-releasing properties of anti-tuberculosis drugs composite in coating material HRZ/PLGA: a study in rats |
| Received:June 12, 2016 Revised:July 06, 2016 |
| English Keywords:Spinal tuberculosis Anti-TB drug Poly(lactic-co-glycolic acid) In vivo Slow-release Rat |
| Fund:国家自然科学基金项目（代码：81360275）；宁夏自然科学基金项目（代码：NZ13131） |
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| English Abstract: |
| 【Abstract】 Objectives: To observe the sustained-release properties of isoniazid(H), rifampicin(R), pyrazinamide(Z) anti-tuberculosis drugs composite/poly(lactic acid-glycolic acid) in coating material(HRZ/PLGA) in rats. Methods: Eighty-four SD adult rats were divided into three groups randomly: HRZ/PLGA group(group A), HRZ group(group B) and the blank copolymer group(group C). Four rats in each group were anesthetized respectively at 1d, 3d, 1w, 2w, 4w, 6w and 8w after surgery, 5ml blood sample was taken through vena cava in each rat. Then rats were killed, and 1cm muscle around the surgery site was obtained. High performance liquid chromatography(HPLC) was applied to detect H, R, Z concentration in the muscle and serum. Liver and kidney functions(AST、ALT、Ur、Cr) were detected at 1w and 4w after surgery, the histopathological changes was observed in muscle tissues of surgery site at 2w and 6w after surgery. Results: In group A, H, R, Z reached the highest drug concentration in muscle and plasma at 3d after surgery, and tended to show a stable descent speed after 2w. The H, R, Z concentrations of group A in muscle were 0.87, 0.92, 1.61μg/g at 8w, which were 10 times as high as their minimum inhibitory concentrations(MIC). The H, R, Z concentrations of group B in muscle reached the highest at 3d after surgery, and dropped sharply, which became undetectable at 4w after surgery. H, R, Z were undetectable in the muscle and plasma of group C. The difference of drug concentration in the muscle and plasma of group A was statistically significant(P<0.05)in the paired t test. In group A, B, C, all the indexes of liver and kidney before surgery, at 1w, and at 4w had no statistical difference(P>0.05). In group A and C, the histopathological of muscle tissues showed some inflammatory cells and empty package, which produced by the degradation of PLGA. The three groups did not have obvious inflammation cell and cell damage. Conclusions: HRZ/PLGA can be sustained and gently released with satisfactory biocompatibility and plasticity in rats. This study provides a new method for local effective administration with combined autologous bone after spinal tuberculosis clearing. |
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