人同种异体骨载异烟肼-壳聚糖缓释微球的制备和体内外释药特性☆

背景：壳聚糖微球具有良好的生物相容性及抗菌活性，被广泛地运用于各种药物缓释系统中。 目的：制备人同种异体骨载异烟肼-壳聚糖微球，并分析其体内释药性能。 方法：用喷雾干燥法制备异烟肼-壳聚糖微球，进行体外45 d的药物释放实验。将单独装载异烟肼的异体骨块(对照组)和装载异烟肼-壳聚糖微球的异体骨块(实验组)分别植入家兔两侧髂骨，采用高效液相色谱法检测药物体内释放情况。 结果与结论：异烟肼-壳聚糖微球外观呈圆形、表面光滑、分散良好；平均粒径(3.33±0.9) μm，载药率(16.25±1.24)%。体外药物释放实验显示无突释现象，24 h释放20%左右，45 d释放76%，释放曲线较平缓，释放稳定；数学模型拟合符合Ritger-Peppas模型。实验组异烟肼浓度在前28 d内缓慢升高，其后缓慢下降，持续56 d以上，浓度38.50~155.75 µg/g；对照组异烟肼浓度在1周左右达高峰，为1982.5 µg/g，21 d后骨块周围药物不能测到。说明异烟肼-壳聚糖缓释微球在体内外均可以缓慢平稳释放异烟肼，且持续时间长。提示人同种异体骨载异烟肼-壳聚糖缓释微球复合体可以作为骨结核病灶清除后的一种置入材料，在提供机械支持的同时进行长时间的局部化疗。

Preparation and release in vitro and in vivo of isoniazid-chitosan sustained release microsphere-loaded human allogeneic bone

BACKGROUND: Chitosan microspheres are widely used in various drug sustained release systems because of their good biocompatibility and antibacterial activity. OBJECTIVE: To study the preparation and release in vivo of isoniazid-chitosan microsphere-loaded human allogeneic bone. METHODS: After the preparation of the isoniazid-chitosan microspheres (ICMs) by spray-drying process, a 45-day in vitro drug release experiment was carried out. Isoniazid-loaded human allogeneic bone grafts (control group) and ICMs-loaded human allogeneic bone grafts (experimental group) were respectively implanted into both sides of the iliac in rabbits. The drug release characteristics in vivo were determined by high efficiency liquid chromatography. RESULTS AND CONCLUSION: The appearances of ICMs were round, smooth and well-dispersed. Their average diameter and drug-loading rate were (3.33±0.9) μm and (16.25±1.24)% respectively. There was no burst release in vitro. The release quantity was about 20% of total amount at 24 hours, and about 76% at 45 days. The release curve was flat. The drug release was stable. Mathematical model was in line with Ritger-Peppas model. In the experimental group, the concentration of isoniazid was slowly increased at first 28 days, and then slowly decreased and lasted for more than 56 days in vivo. The concentration range was 38.05-155.75 µg/g. In the control group, the isoniazid concentration reached a peak 1982.5 ug/g in about 1 week, and the isoniazid could not be detected around the bone after 21 days. The ICMs have the characteristics of slow isoniazid releasing both in vitro and in vivo, and the release can last for a long time. ICMs-loaded bone can be used as an implanted material, which can provide mechanical support and long time local chemotherapy after the operation of bone tuberculosis.