抗结核药物复合支架的制备及其性能研究

Preparation and property of anti-tuberculosis drug carrying composite scaffold

中文关键词:  脊柱结核  抗结核药  药物载体  乳酸-羟基乙酸共聚物  磷酸三钙

英文关键词:Bone tuberculosis  Anti-TB drugs  Drug carriers  Poly(lactic-co-glycolic)  Tri-calcium phosphate

中文摘要:

  【摘要】 目的：制备抗结核药物复合支架，并观察其载药性能、药物释放性能和组织相容性。方法：应用乳酸-羟基乙酸共聚物（PLGA）、磷酸三钙（β-TCP）、异烟肼（INH），通过结合相分离/粒子沥滤法制备成复合药物支架。采用扫描电镜观察支架的形貌；测定支架的孔隙率；在体外测定支架的生物力学强度、载药率、包封率以及药物释放特性；将复合支架（PLGA/β-TCP/INH）埋入大鼠肌肉中，4周后取材固定、染色行组织切片观察其组织相容性。结果：PLGA/β-TCP/INH复合支架表面及内部呈均匀多孔状，孔隙分布较均匀，在大孔的周围布满了相互贯通的微孔，外形多为近似圆形，大孔直径约150~300μm，平均222±23μm，小孔直径约10μm；孔隙率为（86±3）%；抗压强度为1.93±0.65MPa，药物包封率为（66.73±2.65）%；在体外药物释放过程较平稳，其释放曲线较平滑；组织学检查显示埋入大鼠肌肉中4周支架周围组织正常，细胞无变性坏死。结论：PLGA/β-TCP/INH复合支架具有良好的孔隙率、力学强度、释药特性和组织相容性，有望在脊柱结核病灶清除术后利用其修复骨缺损的同时发挥局部抗结核治疗作用。

英文摘要:

  【Abstract】 Objectives: To prepare composite scaffold and investigate its drug-loaded property, drug delivery and biocompatibility. Methods: The porous poly(lactic-co-glycolic)/tri-calcium phosphate/anti-tuberculosis drug (INH) composite scaffold was prepared by combining particle leaching and phase separation technique. The morphology and the structure of scaffold were observed by SEM. The compressive strength and porosity were measured in vitro. INH release behavior, drug loading and encapsulation efficiency of scaffold were determined by ultraviolet spectrophotometry. The scaffolds were implanted into the SD rats, and gross observation and histology assay were conducted 4 weeks after operation. Results: It could be seen that the scaffold possessed a highly interconnected porous structure with the diameter of macro-pore about 150-300μm, and the average diameter was about 222±23μm, and a lot of micro-pores with diameter of about 10μm were found in the wall of intro-and inter-macro-pores. The porous composite scaffold possessed good physical properties with 1.93±0.65MPa compressive strength and (86±3)% porosity and (66.73±2.65)% encapsulation. Drug release process was stable in vitro and the release curve was smooth. Surrounding tissue was normal in vivo with no degeneration and necrosis of cells. Conclusions: The porous composite scaffold perceives good biomechanical properties, porosity, INH release and biocompatibility, which can be used as bone repair as well as anti-tuberculosis material after debridement.