复合三联抗结核药聚乳酸-羟基乙酸缓释微球体内缓释实验研究

Triple anti-tuberculosis drug polylactic acid-glycolic acid microsphere and its slow-release in vivo, an experimental study

中文关键词:  抗结核药  聚乳酸-羟基乙酸微球  体内缓释

英文关键词:Anti-TB drug  PLGA microsphere  Slow-release in vivo

中文摘要:

  【摘要】 目的：观察载异烟肼（H）、利福平（R）、吡嗪酰胺（Z）复合抗结核药/聚乳酸-羟基乙酸共聚物缓释微球在大鼠体内的缓释特性。方法：选取SD雄性成年大鼠84只，随机分成A、B、C三组，分别设为载药微球组、空白微球组、空白组，于术后1d、3d、1周、2周、4周、6周、8周时分别处死各组4只大鼠，处死时取微球周边1cm肌肉组织和腹腔静脉血5ml，应用高效液相色谱法检测肌肉组织和血清中三种药物浓度；在1周、4周时检测肝、肾功能，留取肝、肾组织观察其组织病理学变化。结果：术后3d时A组中肌肉和血浆中HRZ的药物浓度达到最高，1周后药物的浓度趋于稳定；8周时肌肉组织中HRZ的浓度分别为0.56、0.63、1.51μg/g，均达到了各自的10倍最低有效抑菌浓度，血浆中HRZ浓度分别为0.112、0.046、0.189μg/ml，肌肉中药物浓度和血浆中药物浓度行配对t检验，差异有统计学意义（P<0.05）；B、C两组肌肉及血浆中均未检测出HRZ。在1、4周时，对三组大鼠肝、肾功能相关指标进行检测，A与C、A与B、B与C组间两两比较t检验，肝、肾功能各项指标在各检测点均无统计学差异（P>0.05）；A、B、C三组大鼠肝、肾组织病理学检查未见明显损伤。结论：HRZ/PLGA微球具有缓慢、平稳释放药物的特性，具有良好的组织生物相容性，可直接植入体内实现局部给药和缓释长程治疗的双重效果。

英文摘要:

  【Abstract】 Objectives: To observe the isoniazid(H), rifampicin(R), pyrazinamide(Z) composite anti-tuberculosis drug/polylactic acid-glycolic acid copolymer microsphere and its slow-release characteristics in rats. Methods: 84 SD adult male rats were divided into three groups randomly, carrier drug microsphere group(group A), blank microsphere group(group B) and blank group(group C). At postoperative 1d, 3d, 1 week, 2 weeks, 4 weeks, 6 wweeks and 8 weeks, 4 rats in each group were undertaken to death, 1cm muscle around the microsphere was cut down and 5ml blood sample through vena cava was collected, high performance liquid chromatography(HPLC) was used to detect HRZ concentration in the muscle and serum. The liver and kidney function, as well as the histopathological changes in liver and kidney tissues were tested in the first and fourth week. Results: At the 3rd day after surgery in group A, HRZ reached the maximun in muscle and plasma and it tended to be stable after 1 week. The HRZ concentrations of group A in the muscle were 0.56, 0.63, 1.51μg/g respectively, which were 10 times as much as their minimum inhibitory concentration(MIC) in the eighth week. The blood concentrations of HRZ were 0.112, 0.046, 0.189μg/g respectively, drug concentration in muscle and plasma drug concentration were performed by the paired t test, the difference was statistically significant(P<0.05). While it was not detected in the muscle and plasma in group B and C. In the first and fourth week of postoperation, after pairwise comparison t test, liver and renal function be?鄄tween group A and C, A and B, B and C related indicators, showed no statistical difference(P>0.05). The liv?鄄er and kidney histopathological examination of group A, B, C showed no obvious damages. Conclusions: HRZ/PLGA microsphere can be implanted directly for local drug delivery and slow-release, due to its smooth, slow release and good biocompatibility characteristics.