多西他赛混合胶束的制备及其性能评价
发布时间：2018-10-09 11:01
【摘要】：目的为提高难溶性药物多西他赛的水溶性,制备多西他赛-聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(soluplus)-聚乙二醇-15-羟基硬脂酸酯(solutol HS15)混合胶束(docetaxel mixed micelles,DTX-MMs),并对其性质进行评价。方法以soluplus和solutol HS15作为两亲性载体材料,采用薄膜分散法制备DTX-MMs;利用马尔文激光粒度仪测定胶束的粒径及分布;采用透射电镜观察混合胶束的形态;采用高效液相色谱法测定混合胶束的包封率和载药量;采用芘荧光探针法测定混合胶束的临界胶束浓度;以自制多西他赛注射液为对照,比较两种制剂的体内外性质差异。结果由薄膜分散法制备的混合胶束的包封率和载药量分别为89.91%和4.658%,平均粒径为(72.54±2.2)nm,多分散系数为0.16±0.036;透射电镜下观察到混合胶束呈球形、分散良好;测得的临界胶束质量浓度值为(6.76×10~(-2))g·L~(-1);与多西他赛注射剂相比,混合胶束具有一定的缓释能力,无溶血现象,药时曲线下面积(AUC_(0-t))提高了2.638倍。结论采用薄膜分散法制备的混合胶束,粒径小,包封率高,稳定性好,可显著提高多西他赛在水中的溶解度,具有良好的体内外性能。
[Abstract]:Objective to improve the water solubility of docetaxel, an insoluble drug, The mixed micelle (docetaxel mixed micelles,DTX-MMs of docetase-polycaprolactam poly (vinyl acetate)-polyethylene glycol grafted copolymer (soluplus)-polyethylene glycol-15-hydroxystearate (solutol HS15) was prepared and its properties were evaluated. Methods soluplus and solutol HS15 were used as amphiphilic carrier materials, DTX-MMs; was prepared by thin-film dispersion method, the particle size and distribution of micelles were measured by Ma Erwen laser particle size analyzer, and the morphology of mixed micelles was observed by transmission electron microscope (TEM). The entrapment efficiency and drug loading of mixed micelles were determined by HPLC, the critical micelle concentration of mixed micelles was determined by pyrene fluorescence probe method, and the in vitro and in vivo properties of the two preparations were compared with those of docetaxel injection. Results the entrapment efficiency and drug loading of the mixed micelles prepared by the thin film dispersion method were 89.91% and 4.658, respectively. The average particle size was (72.54 卤2.2) nm, polydispersity coefficient was 0.16 卤0.036. Under transmission electron microscope, the mixed micelles were spherical and well dispersed. The critical micelle mass concentration was (6.76 脳 10 ~ (-2) g L ~ (-1). Compared with docetaxel injection, the mixed micelle had a certain sustained release ability, no hemolysis, and the area under the curve (AUC_ (0-t) increased 2.638 times. Conclusion the mixed micelles prepared by thin-film dispersion method have small particle size, high entrapment efficiency and good stability, which can significantly improve the solubility of docetaxel in water and have good properties in vivo and in vitro.
【作者单位】： 沈阳药科大学药学院;
【基金】：辽宁省自然科学基金资助项目(2015020749) 沈阳药科大学创新创业训练计划项目(201610163051)
【分类号】：R943
，
本文编号：2259090
[Abstract]:Objective to improve the water solubility of docetaxel, an insoluble drug, The mixed micelle (docetaxel mixed micelles,DTX-MMs of docetase-polycaprolactam poly (vinyl acetate)-polyethylene glycol grafted copolymer (soluplus)-polyethylene glycol-15-hydroxystearate (solutol HS15) was prepared and its properties were evaluated. Methods soluplus and solutol HS15 were used as amphiphilic carrier materials, DTX-MMs; was prepared by thin-film dispersion method, the particle size and distribution of micelles were measured by Ma Erwen laser particle size analyzer, and the morphology of mixed micelles was observed by transmission electron microscope (TEM). The entrapment efficiency and drug loading of mixed micelles were determined by HPLC, the critical micelle concentration of mixed micelles was determined by pyrene fluorescence probe method, and the in vitro and in vivo properties of the two preparations were compared with those of docetaxel injection. Results the entrapment efficiency and drug loading of the mixed micelles prepared by the thin film dispersion method were 89.91% and 4.658, respectively. The average particle size was (72.54 卤2.2) nm, polydispersity coefficient was 0.16 卤0.036. Under transmission electron microscope, the mixed micelles were spherical and well dispersed. The critical micelle mass concentration was (6.76 脳 10 ~ (-2) g L ~ (-1). Compared with docetaxel injection, the mixed micelle had a certain sustained release ability, no hemolysis, and the area under the curve (AUC_ (0-t) increased 2.638 times. Conclusion the mixed micelles prepared by thin-film dispersion method have small particle size, high entrapment efficiency and good stability, which can significantly improve the solubility of docetaxel in water and have good properties in vivo and in vitro.
【作者单位】： 沈阳药科大学药学院;
【基金】：辽宁省自然科学基金资助项目(2015020749) 沈阳药科大学创新创业训练计划项目(201610163051)
【分类号】：R943
，
本文编号：2259090
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