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目的:观察复合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)三联抗结核药的聚乳酸-羟基乙酸(PLGA)涂层材料(HRZ/PLGA)在大鼠体内的释药特性。方法:将84只成年SD大鼠随机分为A、B、C三组,每组28只。A组为复合抗结核药HRZ/PLGA涂层材料植入组;B组为抗结核药HRZ植入组;C组为空白未载药PLGA涂层材料植入组,于术后1d、3d、1w、2w、4w、6w、8w时分别麻醉各组大鼠4只,抽取腹腔静脉血液5ml,处死后取体内植入材料或药物周边1cm的肌肉组织,应用高效液相色谱法(HPLC)检测肌肉组织及血清中H、R、Z三种药物的浓度,并于1w、4w时取血检测肝、肾功(AST、ALT、Ur、Cr),2w及6w时取植入局部肌肉组织进行形态学观察。结果:A组在术后3d时HRZ/PLGA涂层材料周边肌肉组织中三药浓度均达最高,2w后药物浓度下降趋势平稳,8w时H、R、Z三药平均浓度分别为0.87、0.92、1.61μg/g,均能达到各自10倍最低抑菌浓度(MIC);B组在术后3d时植入HRZ周边肌肉组织中三药物浓度均达最高,但药物浓度下降较快,4w时三种药物均不能检测到;C组不能检测到三种药物。A组肌肉检测药物浓度曲线较B组明显平稳、长程。A组静脉血中三种药物浓度明显低于植入HRZ/PLGA涂层材料周边的肌肉组织(P<0.05)。术后1w、4w时各组AST、ALT、Ur、Cr与术前比较差异均无统计学意义(P>0.05)。2w时A组及C组植入局部肌肉组织HE染色观察镜下见炎症细胞及PLGA降解产生空泡存在,6w时炎症细胞及空泡减少,A、B、C三组未见明显细胞坏死。结论:HRZ/PLGA涂层材料在SD大鼠体内释药平稳,持续时间较长,可实现体内局部用药的有效缓释;直接植入体内后组织生物相容性及可塑形性良好,为脊柱结核病灶清除后复合自体骨的局部有效给药提供了新方法。
OBJECTIVE: To observe the effect of polylactic-co-glycolic acid (PLGA) coating material (HRZ / PLGA) combined with isoniazid (H), rifampin (R) and pyrazinamide (Z) Drug release characteristics. Methods: Eighty - four adult SD rats were randomly divided into A, B and C groups, 28 in each. Group A was HRZ / PLGA coating material with composite antituberculosis drugs; group B was HRZ implantation with anti-TB drugs; group C was blank PLGA-coated material, Four rats in each group were anesthetized at 1w, 2w, 4w, 6w and 8w respectively. 5ml of abdominal venous blood was drawn. After instilled, 1cm of muscle tissue was implanted with material or drug, and detected by high performance liquid chromatography (HPLC) Muscle, liver and renal function (AST, ALT, Ur, Cr) were measured at 1w and 4w, and local muscle tissue was obtained at 2w and 6w Morphological observation. Results: The concentration of three drugs in the muscle tissue around the HRZ / PLGA coating material reached the peak at 3 days after operation, and the drug concentration decreased steadily after 2 weeks. The average concentrations of three drugs H, R and Z at 8 weeks were 0.87 and 0.92 , 1.61μg / g respectively, all reached 10 times the minimum inhibitory concentration (MIC). Group B had the highest concentration of all three drugs in the muscle tissue around HRZ at 3 days after operation, but the drug concentration dropped rapidly at 4w Three drugs can not be detected; C group can not detect three drugs. Group A muscle test drug concentration curve was significantly stable than the B group, long-term. The concentration of the three drugs in the venous blood of group A was significantly lower than that of the muscle tissue around the HRZ / PLGA coated material (P <0.05). There was no significant difference in AST, ALT, Ur, Cr between the groups at 1w and 4w after operation (P> 0.05). At 2w, the local muscle tissue of group A and group C were stained by HE, and inflammatory cells and vacuolated PLGA were observed under microscope. At 6 weeks, the number of inflammatory cells and vacuoles decreased, and no obvious cell necrosis was found in group A, B and C. CONCLUSION: The HRZ / PLGA coating material is stable and sustained for a long time in SD rats, which can effectively release the local drug in vivo. The biocompatibility and plasticity of the HRZ / A New Approach to Local Efficacious Administration of Composite Autologous Bone After Tuberculosis Lesions.