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

English Keywords:Anti-TB drug  PLGA microsphere  Slow-release in vivo

English Abstract:

  【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.