INH-PZA-PLGA缓释微球制备及体外释药性能的研究

发布时间：2018-01-23 22:28

本文关键词： 脊柱结核 INH-PZA-PLGA缓释微球体外释药性能　出处：《安徽医科大学学报》2016年01期 　论文类型：期刊论文

【摘要】：目的研究异烟肼(INH)、吡嗪酰胺乳酸(PZA)-羟基乙酸共聚物(PLGA)微球的制备及体外释药特性。方法以PLGA为载体,采用复乳-溶剂挥发法制备INH-PZA-PLGA微球;扫描电子显微镜(SEM)观察INH-PZA-PLGA微球形态特征;计算INH-PZA-PLGA微球中INH、PZA的载药量、包封率;高效液相色谱法(HPLC)检测INH-PZA-PLGA微球在不同时段模拟体液中INH、PZA的药物浓度,观察其是否均大于10倍最小抑菌浓度(MIC),计算其各阶段释药量、累计释药度并拟合药物体外释放数学方程并观察其体外释药特性。结果 INH-PZA-PLGA微球成球规整、分布均匀、表面光滑、分散性好,平均粒径为(11.04±0.4)μm,INH和PZA的载药量分别为(21.78±0.27)%、(24.91±0.16)%,包封率分别为(58.52±1.65)%、(72.26±1.28)%。INHPZA-PLGA微球中INH突释现象较PZA突释现象明显,46 d INH累计释放量93.01%,PZA累计释放量77.40%。前9 d两种药物释放规律拟合Higuchi曲线的R~2值最大,可认为两种药物按从高浓度向低浓度的规律释放;12 d后两种药物拟合零级曲线的R~2值最大,可认为两种药物按等量的规律释放。结论 INH-PZA-PLGA微球具有良好的体外药物缓释性能,阶段释放量均大于10倍的MIC,理论上可达到体内杀死结核杆菌的浓度,为脊柱结核术后局部给药研究奠定基础。
[Abstract]:Objective to study the preparation and in vitro release characteristics of isoniazid (INH), pyrazinamide lactic acid (PZA) -glycolic acid (PGA) microspheres. Methods PLGA was used as the carrier. INH-PZA-PLGA microspheres were prepared by the method of compound emulsion and solvent volatilization. The morphological characteristics of INH-PZA-PLGA microspheres were observed by scanning electron microscopy (SEM). The drug loading and encapsulation efficiency of INH-PZA-PLGA microspheres were calculated. High performance liquid chromatography (HPLC) was used to detect the concentration of INH-PZA-PLGA microspheres in simulated body fluid. Observe whether they are more than 10 times the minimum inhibitory concentration (MIC) and calculate the drug release amount in each stage. Results INH-PZA-PLGA microspheres were spherical, uniform, smooth and dispersive. The average particle size was 11.04 卤0.4 渭 m for PZA and 21.78 卤0.27 渭 m for INH and 24.91 卤0.16%, respectively. The entrapment efficiency was 58.52 卤1.65 and 72.26 卤1.28, respectively. The sudden release of INH in INHPZA-PLGA microspheres was more obvious than that in PZA. The accumulative release of INH was 93.01 and 77.400.The R2 value of Higuchi curve fitted to the first 9 days was the largest. It can be concluded that the two drugs are released from high concentration to low concentration. After 12 days, the R2 value of the two drugs fitted to zero order curve was the largest, and the two drugs were released according to the same quantity. Conclusion INH-PZA-PLGA microspheres have good drug release ability in vitro. The release amount of MICM is more than 10 times, which can reach the concentration of killing Mycobacterium tuberculosis in vivo theoretically, and lay a foundation for the study of local administration of spinal tuberculosis after operation.
【作者单位】：宁夏医科大学总医院脊柱骨科;宁夏医科大学研究生学院;宁夏医科大学总医院创伤骨科;宁夏医科大学医学科学技术研究中心;
【基金】：国家自然科学基金(编号:81360275) 宁夏自然科学基金(编号:NZ13131) 宁夏医科大学校级项目(编号:XT20)
【分类号】：R943;R96
【正文快照】： 2015-09-30接收随着脊柱结核生物材料的发展,其疗效明显改善,但药物化疗仍是治疗的基础和根本[1-2]。药物疗效取决于病灶局部药物浓度,由于病灶部位硬化死骨形成,局部血运差,常规抗结核药物化疗难以达到有效杀菌药物浓度,并易导致耐药结核病的出现,已成药物化疗难以奏效、疾病

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