载利福喷丁与利奈唑胺聚乳酸—羟基乙酸缓释微球肺部靶向给药系统的研究

发布时间：2018-03-28 21:38

本文选题：利福喷丁　切入点：利奈唑胺　出处：《山西医科大学》2017年硕士论文

【摘要】：目的:本文以利福喷丁(Rifapentine,RIF)和利奈唑胺(Linezolid,LZD)为模型药物,以聚乳酸-羟基乙酸[poly(lactic-co-glycolic acid),PLGA]为载体,制备了载利福喷丁与利奈唑胺聚乳酸-羟基乙酸缓释微球(Rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid)microspheres,RLPMs),用于解决肺结核支气管镜介入治疗时所选用的药物缓释效果差和有效药物浓度维持时间短的问题。方法:首先,建立利福喷丁与利奈唑胺高效液相色谱检测法(high-performance liquid chromatography,HPLC),绘制其标准曲线,用于检测利福喷丁与利奈唑胺药物浓度。然后,采用水包油(Oil-in-Water,O/W)的乳化溶剂挥发法制备载药微球,并通过对不同制备工艺下所制备微球的形态、粒径大小、载药量和包封率等理化特性进行考察,筛选出最佳制备工艺。最后,对缓释微球的体外释放特性、肺内粘附性、留滞特性以及支气管和肺组织病理观察进行了评价。结果:最佳制备工艺所制备的微球呈球形,表面有圆形凹陷,微球粒径大小为27.38±1.28μm,利福喷丁与利奈唑胺的载药量分别为18.51±0.26%和8.42±0.24%,包封率分别为55.53±0.78%和16.87±0.47%(n=3)。在体外释放试验的突释期内,利福喷丁3d内释放21.37±0.68%,利奈唑胺1d内释放43.56±2.54%,随后二者进入平稳释放期,最终利福喷丁与利奈唑胺14d累计释放率分别为27.61±1.52%和51.01±3.31%(n=3)。通过肺内粘附性试验、滞留性试验以及支气管和肺组织病理观察,缓释微球能够在犬支气管黏膜表面缓慢释放并滞留20d,并且不会对支气管黏膜造成损害,安全可靠。结论:本研究所制备的微球具有明显的缓释效果以及能有效滞留于支气管黏膜表面,安全可靠,达到了实验预期设计的目标。
[Abstract]:Objective: in this paper, rifapentine rifapentine rifapentine (rifapentine) and linazolidine (LZD) were used as model drugs and poly(lactic-co-glycolic acidoglycolic acid (poly(lactic-co-glycolic) was used as the carrier. Rifapentine-linezolid-loaded poly(lactic acid-co-glycolic microspheres-RLPMs were prepared with rifapentine-linezolid-loaded poly(lactic acid-co-glycolic microspheres, which were used to solve the problem of low sustained release effect and short duration of effective drug concentration in bronchointerventional therapy for pulmonary tuberculosis. Methods: first of all, A high performance liquid chromatographic HPLC method was established for the determination of rifapentine and linazolamide. The standard curve was drawn for the determination of the concentration of rifapentine and linazolamide. Then, the emulsified solvent volatilization method was used to prepare the drug loaded microspheres. The physical and chemical properties such as morphology, particle size, drug loading and encapsulation efficiency of the microspheres prepared under different preparation processes were investigated, and the best preparation process was obtained. Finally, the in vitro release characteristics and intrapulmonary adhesion of sustained-release microspheres were studied. Results: the microspheres prepared by the best preparation technique were spherical and had a circular depression on the surface. The particle size of the microspheres was 27.38 卤1.28 渭 m, the drug loading of rifapentine and linazolamide were 18.51 卤0.26% and 8.42 卤0.24.The entrapment rates were 55.53 卤0.78% and 16.87 卤0.47% respectively. The release rate of rifapentine was 21.37 卤0.68 in 3 days, and that of linazolamine was 43.56 卤2.54 in one day. The cumulative release rates of rifapentine and renazolamide in 14 days were 27.61 卤1.52% and 51.01 卤3.31% respectively. Retention test and pathological observation of bronchi and lung tissue showed that the sustained release microspheres could be released slowly and remained on the surface of canine bronchial mucosa for 20 days without causing damage to the bronchial mucosa. Conclusion: the microspheres prepared in this study have obvious slow-release effect and can effectively stay on the surface of bronchial mucosa.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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