万古霉素壳聚糖缓释微球的制备及其体外释药特性和抑菌作用研究

Preparation of Vancomycin-loaded Chitosan Sustained-release Microspheres and Its Drug Release in vitro and Antibacterial Effect

目的:制备万古霉素壳聚糖缓释微球,考察其体外释药特性和抑菌作用。方法:采用乳化交联法制备万古霉素壳聚糖缓释微球,观察微球的粒径分布及形态;应用紫外分光光度法测定微球药物含量,计算载药量及包封率;通过体外释放试验,比较其与盐酸万古霉素24 h内的体外释药情况,考察其7 d内的累积释放度(Q);通过体外抑菌试验观察其作用20 d对金黄色葡萄球菌抑菌圈直径的影响。结果:所制万古霉素壳聚糖缓释微球呈圆球形,表面圆整,无明显凹凸和孔隙,平均粒径为(165.6±19.7)μm,平均载药量为(32.6±3.2)%,平均包封率为(53.8±6.3)%,Q_(7d)为82.7%;其与盐酸万古霉素的Q_(2h)分别为18.6%、91.3%;其作用1 d时的抑菌圈直径>3 cm,随其作用时间的延长,抑菌圈直径逐渐缩小。结论:成功制得万古霉素壳聚糖缓释微球,其体外缓释效果明显,且具有良好的体外抑菌作用。

OBJECTIVE： To prepare vancomycin-loaded chitosan sustained-release microspheres and to study its drug release and antibacterial effects in vitro. METHODS： The emulsion cross-linking was used to prepare vancomycin-loaded chitosan sus- tained-release microspheres, and the particle size and morphology of microspheres were observed. The contents of vancomycin in microspheres was determined by UV spectrophotometry, and drug-loading amount of entrapment efficiency were calculated. Drug release of prepared microspheres and vancomycin hydrochloride within 24 h were compared by release trial in vitro, and then its ac- cumulative release rate （Q） within 7 d was investigated. The effects of prepared microspheres on the diameter of inhibition zone to Staphylococcus aureus after treated for 20 d were observed through in vitro antibacterial test. RESULTS： The microspheres were spherical and complete round without obvious bump and pore. The average particle size of the microspheres was （165.6 ±19.7）μm; average drug-loading amount was （32.6 ±3.2） % ; average encapsulation efficiency was （53.8± 6.3） % ; Q7 d was 82.7%. Q2 h of prepared microspheres and vancomycin hydrochloride were 18.6% and 91.3%. The diameter of inhibition zone was higher than 3 cm after treated for 1 d, and then decreased gradually as time. CONCLUSIONS： Vancomycin-loaded chitosan sustained-release microspheres can be prepared successfully, and show obvious in vitro sustained-release effect and antibacterial effects.