中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (6): 911-916.doi: 10.3969/j.issn.2095-4344.2017.06.016

• 药物控释材料 drug delivery materials • 上一篇    下一篇

聚乳酸/聚乙醇酸共聚物涂饰载三联抗结核药人工骨体外释药对比

王  骞1，刘海涛2，施建党3，王自立3，耿广起3，牛宁奎3，王  洁4，闫军法3
  

  1. 1美国南佛罗里达大学医学院  33612 坦帕；宁夏医科大学总医院，2创伤骨科，3脊柱骨科，宁夏回族自治区银川市  750004；4宁夏医科大学科学技术实验中心，宁夏回族自治区银川市  750004
  • 收稿日期:2017-01-07 出版日期:2017-02-28 发布日期:2017-03-16
  • 通讯作者: 刘海涛，硕士，主治医师。宁夏医科大学总医院创伤骨科，宁夏回族自治区银川市 750004
  • 作者简介:王骞，男，1984年生，汉族，宁夏回族自治区银川市人，2012年美国南弗罗里达大学医学院毕业，硕士，主治医师。 王骞及刘海涛为共同第一作者。
  • 基金资助:

    国家自然科学基金项目(81060149)；宁夏自然科学基金项目(NZ10117，NZ11195)

Comparative study of drug release in vitro of polylactic acid/polyglycolic acid coated triple anti-tuberculosis drug-loading artificial bone

Wang Qian1, Liu Hai-tao2, Shi Jian-dang3, Wang Zi-li3, Geng Guang-qi3, Niu Ning-kui3, Wang Jie4, Yan Jun-fa3 
  

  1. 1School of Pharmacy, University of South Florida, Tampa 33612, USA; 2Department of Traumatic Orthopedics, 3Department of Spine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 4Experimental Center, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2017-01-07 Online:2017-02-28 Published:2017-03-16
  • Contact: Liu Hai-tao, Master, Attending physician, Department of Traumatic Orthopedics, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Wang Qian, Master, Attending physician, School of Pharmacy, University of South Florida, Tampa 33612, USA Wang Qian, Liu Hai-tao, and Shi Jian-dang contributed equally to this work.
  • Supported by:

    the National Natural Science Foundation of China, No. 81060149; the Natural Science Foundation of Ningxia Hui Autonomous Region, No. NZ10117, NZ11195

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被引次数

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摘要：

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文题释义：
聚乳酸/聚乙醇酸共聚物涂饰载三联抗结核药人工骨的特点：是指以硫酸钙/氨基酸聚合物作为药物缓控释体系的载体，植入病灶部位后载体所承载的异烟肼、利福平、吡嗪酰胺能够持续、稳定、高效地缓慢释放，达到修复骨缺损和药物治疗的双重目的，利用复合材料降解吸收时相的不同，既能满足椎间植骨支撑的需要，在自体成骨中缓慢降解实现药物的缓释增加了结核病灶药物浓度。
聚乳酸：是一种新型的生物降解材料，使用可再生的植物资源(如玉米)所提出的淀粉原料制成。淀粉原料经由发酵过程制成乳酸，再通过化学合成转换成聚乳酸。

背景：载三联抗结核药[异烟肼(INH)、利福平(RFP)、吡嗪酰胺(PZA)，HRZ]硫酸钙/聚氨基酸人工骨材料具有较好的释药特性及抗菌活性，但其不足之处亦为存在着突释现象，发生突释的原因是硫酸钙降解过快。
目的：观察聚乳酸/聚乙醇酸共聚物涂饰对载三联抗结核药(HRZ)硫酸钙/聚氨基酸人工骨体外药物释放行为的影响。
方法：避光环境下按照优化配方，制备载药A、B组与非载药组人工骨，载药A组为涂饰聚乳酸/聚乙醇酸共聚物(PLGA)的载三联抗结核药(HRZ)人工骨，B组为未涂饰PLGA的载三联抗结核药的硫酸钙/聚氨基酸人工骨，另设非载药组人工骨，将3组人工骨直接干燥、灭菌后，以模拟体液为介质进行浸泡释放实验。用高效液相色谱法法检测不同时段异烟肼、利福平及吡嗪酰胺3种药物的释放浓度。
结果与结论：载药A组载三联抗结核药人工骨在17周时异烟肼药物释放量占总载药量的43.51%；16周时，利福平与吡嗪酰胺药物释放量占各自总载药量的15.92%和48.42%。载药B组载三联抗结核药人工骨在浸泡7周时异烟肼的药物释放量占总载药量的91.75%；8周时，吡嗪酰胺、利福平药物释放量分别占各自总载药量的88.34%和49.35%。非载药组在有效检测时间段未出现药物峰。结果说明，聚乳酸/聚乙醇酸共聚物涂饰，可以稳定、有效的控制载三联抗结核药硫酸钙/聚氨基酸人工骨的药物释放，增加释放周期时间，使病灶局部药物浓度长时间维持在较高的水平，可以充分发挥载三联抗结核药人工骨局部抗结核的作用。

关键词: 生物材料, 药物控释材料, 三联抗结核药, 硫酸钙/聚氨基酸人工骨, PLGA, 缓释, 高效液相色谱法, 异烟肼, 利福平, 吡嗪酰胺, 突释, 国家自然科学基金

Abstract:

BACKGROUND: Calcium sulfate/polyamino acid artificial bone material carrying triple anti-tuberculosis drugs (isoniazide, rifampicin, pyrazinamide) has good release characteristics and antibacterial activity, but its shortcomings also exist for the phenomenon of burst, due to a faster degradation of calcium sulfate.
OBJECTIVE: To observe the effect of polylactic acid/polyglycolic acid copolymer (PLGA) coating on drug release behavior in vitro of triple anti-tuberculosis drugs containing calcium sulfate/polyamino acid bone.
METHODS: According to the selected optimum recipe, we prepared drug-loading artificial bones and non-drug-loading artificial bones in a dark place. After infiltrating in PLGA, drying and sterilizing, we soaked them in simulated body fluid for drug release experiments. Through high performance liquid chromatography method, the concentrations of isoniazide, rifampicin, pyrazinamide released at different times were observed.
RESULTS AND CONCLUSION: For triple anti-tuberculosis drugs drug artificial bone with no PLGA coating, the drug release of isoniazide accounted for 91.75% of the total drug loading capacity at 7 weeks; the drug releases of rifampicin and pyrazinamide respectively accounted for 88.34% and 49.35% of their own total drug loading capacity at 8 weeks. For triple anti-tuberculosis drug artificial bone with PLGA coating, the drug release of isoniazide accounted for 43.51% of the total drug loading capacity at 17 weeks; the drug releases of rifampicin and pyrazinamide respectively accounted for 15.92% and 48.42% of their own total drug loading capacity at 16 weeks. For blank control group, the drug peak was not noticed in effective detection period. These findings indicate that PLGA coated triple anti-tuberculosis drug-loading calcium sulfate/polyamino acid artificial bone can control drug release, increase the release period and maintain a high level of drug concentration in local lesion for a long time, so as to give full play to the anti-tuberculosis function of triple anti-tuberculosis drug loading artificial bone.

Key words: Tissue Engineering, Biocompatible Materials, Calcium Sulfate

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