涂饰PLGA载三联抗痨药人工骨的体外释药研究

Drug Sustained- release of Artificial Bone with PLGA Coating Triple Anti- TB Drugs in Vitro

目的探讨涂饰聚乳酸/聚乙醇酸共聚物(PLGA)的载三联抗痨药硫酸钙/聚氨基酸人工骨体外药物释放情况。方法避光环境下按照优化配方,制备载药与非载药人工骨,用PLGA溶液浸润涂饰,干燥、灭菌后,以模拟体液为介质进行浸泡释放实验。用HPLC法检测不同时段异烟肼(INH)、利福平(RFP)、吡嗪酰胺(PZA)三种药物的释放浓度。结果涂饰PLGA载三联抗痨药人工骨在第3天的释药浓度:INH为(62.32±1.20)μg·m L-1,RFP为(2.84±0.32)μg·m L-1,PZA为(214.28±9.53)μg·m L-1。INH在第19周的检测浓度为(0.52±0.12)μg·m L-1,后未检测到;RFP第18周的检测浓度为(1.46±0.33)μg·m L-1,后未检测到;PZA第20周的检测浓度为(0.69±0.03)μg·m L-1,后未检测到。涂饰PLGA载三联抗痨药人工骨,在17周时异烟肼的释放量占总载药量的43.51%;16周时,利福平与吡嗪酰胺的释放量占各自总载药量的15.92%、48.42%。空白对照组在有效检测时间段未出现药物峰。结论涂饰PLGA载三联抗痨药硫酸钙/聚氨基酸人工骨,可以稳定缓慢释放药物,使病灶局部的药物浓度维持在较高的水平。

Objective To observe the control release of c alcium sulphate / polyaminoacids bone with polylactic acid / polyglycolic acid copolymer( PLGA) coating triple anti- tuberculosis drugs in vitro. Methods According to optimized formulation,the drug- loaded and non- drug- loaded artificial bones were prepared in the dark environment. Then they were coated with PLGA solution. After drying and sterilizing,they had been soaked in simulated body fluid for the release test. Drug- released concentrations in different periods were measured by HPLC. Three drugs were isoniazid( INH),rifampicin( RFP),pyrazinamide( PZA). Results The released drugs from triple anti- TB drugs artificial bone complex with PLGA coating,after 3 days,the concerntration of INH was( 62. 32 ± 1. 20) μg · m L- 1,RFP was( 2. 84 ± 0. 32) μg · m L- 1,PZA was( 214. 28 ± 9. 53) μg·m L- 1. After 19 weeks,the concentration of INH was( 0. 52 ± 0. 12) μg·m L- 1. After18 weeks,RFP was( 1. 46 ± 0. 33( μg·m L- 1. After 20 weeks,PZA was( 0. 69 ± 0. 03) μg·m L- 1. The released drugs from triple anti- TB drugs artificial bone complex with PLGA coating as follows: isoniazid was43. 51% of total drug- loaded at 17 weeks while at 16 weeks,rifampin was 15. 92% and pyrazinamide was48. 42%. Drug peak did not appear in blank control group during the effect time. Conclusion Artificial bone with PLGA coating rriple anti- tuberculous drugs could release drug stably and slowly and maintain a relative high drug concentration.