局部定向抗结核药物缓释材料在兔桡骨内的释放及分布规律

Release and distribution of anti-tuberculosis drug delivery materials locally oriented in the rabbit radius

背景:聚乳酸-羟基乙酸聚合物作为缓释材料,载药量相对较大且释药时间较长,可随着机体细胞的生长而降解,但其亲水性较差,容易引起无菌性炎症反应,不利用机体恢复。目的:分析新型局部定向抗结核药物缓释材料在兔桡骨内的释放及其分布规律。方法:取新西兰大白兔20只,建立桡骨远端骨缺损模型后随机分组,实验组于骨缺损处置入载异烟肼-利福平聚乳酸-羟基乙酸聚合物/β-磷酸三钙材料,对照组于骨缺损处置入载异烟肼-利福平聚乳酸-羟基乙酸聚合物材料。置入后4,8,12周进行缺损部位X射线检查;置入后12周,进行缺损部位组织学观察,同时检测外周血与局部血药浓度。结果与结论:(1)X射线检查:实验组置入后不同时间点的Lane-Sandhu X射线评分显著高于对照组(P<0.05);(2)组织学观察:实验组缺损部位完全愈合,新生骨小梁之间残留少量缓释材料,材料表面存在明显骨细胞;对照组缺损部位存在新生骨组织且与周围骨组织相互连接,新生骨组织中残留少许缓释材料;(3)血药浓度:实验组置入后不同时间点的外周血与局部血药浓度均高于对照组(P<0.05);(4)结果表明:载异烟肼-利福平聚乳酸-羟基乙酸聚合物/β-磷酸三钙局部定向抗结核药物在兔桡骨内释放效果理想,可长时间稳定释放并在局部保持较高杀菌浓度。

BACKGROUND： Polylactic acid-glycolic acid polymer is a sustained-release material with relatively large drug loading and long-term release abilities that can degrade with cell growth in the body. However, its poor hydrophily easily leads to aseptic inflammation that is detrimental to the body＇s recovery. OBJECTIVE： To study the release and distribution of anti-tuberculosis drug delivery materials locally oriented within the rabbit radius. METHODS： After modeling, 20 New Zealand white rabbits with distal radius bone defect were randomly divided into a control group and an experimental group, which were respectively given implantation of isoniazid-rifampicin polylactic acid-glycolic acid polymer/β-tricalcium phosphate material and isoniazid-rifampicin polylactic acid-glycolic acid polymer into the defect. Then, X-ray examination of the defect region was conducted at weeks 4, 8, 12 post implantation. Histological observation and detection of peripheral blood or local blood concentration were performed at week 12. RESULTS AND CONCLUSION： After implantation, Lane-Sandhu X-ray scores were significantly higher in the experimental group than the control group（P 〈0.05）. The defect in the experimental group was healed completely with less release residual among newborn bone trabeculae and osteocytes were markedly visible on the material surface, while in the control group, new bone tissues were interconnected with the surrounding bone tissues at the defect site, and less release residual was found. Both peripheral blood and local blood concentrations in the experimental group were significantly higher than those in the control group after implantation（P 〈0.05）. To conclude, the anti-tuberculosis drug delivery material, isoniazid-rifampicin polylactic acid-glycolic acid polymer/β-tricalcium phosphate, has ideal release effect that can stably deliver anti-tuberculosis drugs for a long term at a high bactericidal concentration.