多西他赛人血白蛋白微球的制备及体外释药性质的评价

Preparation of human albumin microsphere containing docetaxel and evaluation of in vitro release properties

目的:通过优选工艺条件制备多西他赛人血白蛋白微球,并考察其体外缓释特性。方法:以人血白蛋白为药物载体,采用乳化-化学交联法制备多西他赛蛋白微球,HPLC测定多西他赛的浓度,通过L16(45)正交设计试验考察药质比、交联剂用量、交联时间、搅拌转速、酸碱度等因素对微球载药量和包封率的影响,利用极差分析和方差分析优选最佳工艺条件;扫描电镜观察微球形态;以累积释药百分率为指标考察微球体外释药特性。结果:最佳工艺条件为药质比为1∶7、交联剂用量为2.0mL、交联时间为1.5h、搅拌转速为300r·min-1、反应介质pH值为7.5;以优化工艺制备的微球在扫描电镜下可见为表面光滑的类球体,平均粒径为36.16μm,载药量为(11.74±0.26)%,包封率为(65.24±1.24)%,体外释药模式符合Higuchi方程Q=14.34t1/2+0.21(r=0.994 5),48h体外累积释药百分率为82.8%。结论:本实验通过优化工艺条件,制备完成载药量、包封率和缓释性均较为理想的多西他赛人血蛋白微球。

OBJECTIVE To prepare docetaxel-albumin microsphere via optimized process before investigating slow releasing in vitro. METHODS Docetaxel-albumin microsphere was prepared with human serum albumin as carrier by emulsion-chemical crosslinking, the encapsulation effic!ency and drug loading rate of microsphere were determined by HPLC. The optimal process was selected according to the ratio of m DT/m HSA, consumption of cross-linking agent, cross-linking period, speed of vortex and pH of solution, which were all analyzed Via L16 （45 ） orthogonal array design. The feature of microsphere was observed by e- lectron microscope （SEM）. Extracorporeal drug releasing characteristics were investigated by the cumulative drug releasing per- centage. RF^ULTS The optimal process of preparing microsphere： docetaxel and albumin ratio of 1：7, using 2. 0 mL of cross- linking agent for 1.5 hour at the vortex speed of 300 r · min1 in pH 7. 5 solution. The optimal microsphere was observed as smooth spheroid under the SEM, the mean particle size was 36. 16 μm, the drug loading rate was （11.74 ± 0. 26） and the ecapsulation efficiency was （65.24±1.24）%. In vitro, drug release model was fitted to Higuchi formula Q = 14. 34t1/2± 0. 21 （r = 0. 994 5） and cumulative drug releasing percentage was up to 82. 8% after 48 hours. CONCLUSION Docetaxel-albumin microsphere is prepared by optimal process, with preferable drug loading rate, ecapsulation efficiency and slower releasing rate.