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载替考拉宁治疗骨髓炎症的硼酸盐生物玻璃药物载体的研究

张 欣1, 贾伟涛2, 顾刈非1, 张长青2, 黄文旵1, 王德平1, 3   

  1. 1. 同济大学 材料学院 生物工程与信息技术材料研究所, 上海 200092; 2. 上海市第六人民医院, 上海 200233; 3. 同济大学 教育部先进土木工程重点实验室, 上海 200092
  • 收稿日期:2009-06-22 修回日期:2009-09-18 出版日期:2010-03-20 网络出版日期:2010-03-20

Borate Bioglass Based Drug Delivery of Teicoplanin for Treating Osteomyelitis

ZHANG Xin1, JIA Wei-Tao2, GU Yi-Fei1, ZHANG Chang-Qing2 , HUANG Wen-Hai1, WANG De-Ping1,3

  

  1. 1. Intitute of Bio-engineering and Information Technology Materials, School of Materials Science and Engineering, Tongji University, Shanghai 200092, China; 2. Shanghai Sixth People’s Hospital, Shanghai 200233, China; 3. Key Laboratory of Advanced Civil Engineering Materials, Tongji University, Shanghai 200092, China
  • Received:2009-06-22 Revised:2009-09-18 Published:2010-03-20 Online:2010-03-20

摘要: 本实验制备了用于治疗骨髓炎的以硼酸盐生物活性玻璃为基体负载抗菌素的药物载体系统. 此药物载体系统的固相为硼酸盐生物玻璃, 其组成为6Na2O-8K2O-8MgO-22CaO-54B2O3-2P2O5(mol%); 液相为壳聚糖/柠檬酸/葡萄糖溶液; 所载药物为水溶性药物替考拉宁. 在体外的磷酸盐缓冲溶液(PBS)的浸泡实验中, 对载体系统中的药物释放、机械性能以及玻璃基体的生物降解性进行了测试, 通过高效液相色谱仪测定浸泡溶液中替考拉宁的含量. 实验表明, 这种硼酸盐生物活性玻璃基药物载体系统中的药物缓释可持续30d; 其中, 在缓释的第一周内药物缓释量仅达到72%. 通过Peppas模型对药物缓释行为进行模拟, 证明药物的释放过程符合Fick扩散定律. 实验结果还表明, 经XRD物相分析证实, 这种硼酸盐生物玻璃基体在药物释放的过程中转化为羟基磷灰石(Hydroxyapatite, HA), 显示出药物载体系统的体外生物活性. 在以兔子为动物模型的体内实验中, 药物载体系统治愈了兔子胫骨中的骨髓炎, 而且又促进骨创伤处新骨的生成. 实验证明, 硼酸盐生物活性玻璃是一种既能负载抗菌素药物治疗骨髓炎, 又能促进骨修复的优良的生物材料.

关键词: 硼酸盐玻璃, 药物载体, 替考拉宁, 动力学, 羟基磷灰石

Abstract: A drug delivery system which contains antibiotics for treating osteomyelitis based on a borate bioactive glass was developed. The system was consisted of the borate bioactive glass6Na2O-8K2O-8MgO-22CaO-54B2O3-2P2O5(mol%) as the solid phase, the solution of chitosan, critic acid and glucose as the liquid phase and carried watersoluble teicoplanin as the antibiotics. In vitro test, the drug release behavior, the mechanical properties and the biocompatibility of the drug delivery system were investigated, when the drug delivery device was immersed in phosphate buffer solution (PBS). The drug concentration in PBS were tested by HPLC(High Performance Liquid Chromatography). The drug releasing process could last as long as 30d and 72% of the drug content was released within the first week. The mechanism for the drug releasing from the devices was in accordance with Fick’s diffusion law, when the process was simulated in the Peppas model. The XRD results proved that the bioactive glass material converted into hydroapatite (HA) during the drug release process, indicating that the system had bioactivity in vitro. In vivo test on rabbits, the drug delivery system cured the osteomyelitis in tibial bone, and stimulated the regeneration of tibial bone. The above results proved that the borate bioactive glass was a suitable material for carrying antibiotics to cure osteomyelitis, and for stimulating bone regeneration.

Key words: borate glass, drug carrier, teicoplanin, kinetics, hydroxyapatite

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