加替沙星-聚癸二酸酐局部缓释系统的体内释药特性

Drug release characteristics of gatifloxacin-poly sebacic anhydride local controlled release system

背景:全身大剂量应用抗生素治疗骨感染的不良反应较多,效果不是十分理想,因此探索一种以可降解材料为载体预防骨感染的方法具有很好的应用价值。目的:分析加替沙星-聚癸二酸酐局部缓释系统的体内释药特性。方法:在新西兰大耳白兔右侧膝关节制作3mm×6mm大小的骨窗,植入加替沙星-聚癸二酸酐缓释制剂,术后1,2,3,6,9,12,15,18,25,30d取心脏血、骨组织及骨髓组织标本,以高效液相色谱法测定各组织内加替沙星浓度;扫描电镜观察加替沙星-聚癸二酸酐缓释制剂植入前后的结构变化。结果与结论:加替沙星-聚癸二酸酐缓释制剂植入后,骨髓组织内药物浓度逐渐降低,在第1天出现了一个较高的高峰,第3-15天药棒释放较平稳,15-30d逐渐降低,但在30d末时的药物浓度仍大于对金黄色葡萄球菌的最小抑菌浓度0.1mg/L;骨组织内的药物浓度高峰出现于第3天,其余时间的浓度较平稳,并且均大于0.1mg/L;在同一时间点,血标本中药物浓度小于骨髓组织和骨组织内药物浓度。加替沙星-聚癸二酸酐缓释制剂是表面溶蚀降解,降解残留物为小球状,其内部结构未发生变化,在药物持续释放过程中药棒未发生崩解和碎片化。表明加替沙星-聚癸二酸酐局部缓释制剂具有良好的载药及药物缓释能力。

BACKGROUND：High-dose antibiotics for bone infection have many adverse reactions, and its outcomes are not perfect. Thus, to explore a degradable material as a vector to prevent bone infection is valuable. OBJECTIVE：To study drug release characteristics of gatifloxa-poly sebacic anhydride local control ed release system in vivo. METHODS：A 3 mm × 6 mm bone window was made at right knee joint of New Zealand rabbits. The gatifloxacin-poly sebacic anhydride sustained release preparation was implanted. Heart blood, bone tissue and myeloid tissue specimens were obtained at 1, 2, 3, 6, 9, 12, 15, 18, 25 and 30 days after surgery. High-performance liquid chromatography was utilized to determine gatifloxacin concentration. Scanning electron microscope was employed to observe the structural changes before and after implantation of gatifloxacin-poly sebacic anhydride sustained release preparation. RESULTS AND CONCLUSION：After implantation of gatifloxacin-poly sebacic anhydride sustained release preparation, drug concentration gradual y decreased in the myeloid tissue, peaked at 1 day, stabilized at 3-15 days, gradual y reduced at 15-30 days. However, the drug concentration was stil higher than the minimal inhibitory concentration 0.1 mg/L against Staphylococcus aureus at 30 days. The peak of drug concentration in the bone tissue occurred at 3 days, and stabilized at other days, which was higher than 0.1 mg/L. At the same time point, drug concentration in the blood specimen was lower than that in the myeloid tissue and bone tissue. The degradation of gatifloxacin-poly sebacic anhydride sustained release preparation was surface erosion, and the shape of the degradation residue is smal globular. The change of the internal structure of gatifloxacin-poly sebacic anhydride sustained release preparation was not found. In the drug release procedure, gatifloxacin-poly sebacic anhydride sustained release preparation did not show disintegration or fragmentation. These results indicated that gatifloxacin-poly sebacic anhydride local sustained release preparation has good abilities of drug load and drug release.