异烟肼载体缓释微球的制备及家兔释药特性分析

Preparation of Isoniazid Carrier Sustained-Release Microspheres and Analysis of Drug Release Characteristics in Rabbits

目的:制备异烟肼载体缓释微球并分析其体内外释药特性。方法:于2017年7月至2019年10月深圳市第二人民医院,选择36只雄性家兔作为实验动物模型,采用喷雾干燥法制备异烟肼–壳聚糖微球,观察微球形态,测量微球粒径,计算微球载药率及包封率,分析微球体内外释药特性。结果:异烟肼–壳聚糖微球表面光滑,球粒完整,大小均匀,无粘连,无杂质,分散性良好,没有聚集现象;微球平均粒径(4.73±0.88)μm,载药率(17.45±1.33)%,包封率(47.58±0.86)%;缓释微球体外释药在28 d时释药率达到83%左右,释药平稳;24 h、72 h、1周、3周时,微球组关节滑膜药物浓度明显高于灌胃组、原药组,差异具有统计学意义(P<0.05);微球组0~24 h血液药物浓度波动差值明显低于灌胃组、原药组,差异具有统计学意义(P<0.05)。结论:本研究制备的异烟肼–壳聚糖缓释微球在体内外均可缓慢平稳释放异烟肼,持续时间长,能够作为骨结核病灶清除后的一种置入材料,对术后病灶发挥持久的疗效。

Objective To prepare isoniazid carrier sustained-release microspheres and analyze their in vitro and in vivo drug release characteristics.Methods From July 2017 to October 2019,thirty-six male rabbits were selected as the experimental animal models in Shenzhen second people's hospital,and isoniazid-chitosan microspheres prepared by spray drying.The morphology of the microspheres were observed,the particle size of the microspheres were measured,the drug loading rate and encapsulation efficiency of the microspheres were calculated,and the drug release characteristics of the microspheres in vitro and in vivo were analyzed.Results Isoniazid-chitosan microspheres have smooth surface,intact spherules,uniform size,no adhesion,no impurities,good dispersibility,no aggregation;average particle size of microspheres(4.73±0.88)μm,drug loading rate(17.45±1.33)%,encapsulation efficiency(47.58±0.86)%.The release rate of sustained-release microspheres in vitro was about 83%at 28 days,and the drug release was stable.At 24h,72h,1w,3w,the joint synovial drug concentration in the microsphere group was significantly higher than that in the gavage group and the original drug group.The difference was statistically significant(P<0.05).The fluctuation difference of blood drug concentration in the microsphere group from 0 to 24h was significantly lower than that in the gavage group and the original drug group,and the difference was statistically significant(P<0.05).Conclusion The isoniazid-chitosan sustained-release microspheres prepared in this study can release isoniazid slowly and stably in vivo and in vitro,and last for a long time.It can be used as an implant material after the removal of bone tuberculosis lesions to exert a lasting effect on postoperative lesions.