Cu^2+/DSF共载型给药系统的制备与体外评价  

Preparation and evaluation of Cu/DSF co-loading drug delivery system

作　　者：金晨 侯晔 张宇[1] 唐星[1] JIN Chen;HOU Ye;ZHANG Yu;TANG Xing(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2020年第11期975-981,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的将二油酰磷脂酸(dioleoylphosphatydic acid,DOPA)包衣的磷酸铜(copper phosphate,CuP)纳米粒(CuP/DOPA,约20 nm)和双硫仑(disulfiram,DSF)共载于脂质微球(lipid microspheres,LMs,约200 nm)中,并包埋在透明质酸热敏凝胶内,制备Cu^2+/DSF共载型给药系统并评价其性能。方法通过高压乳匀法将DSF与采用乳化分散法制备的CuP/DOPA共载入LMs中并分散在透明质酸热敏凝胶中得到Cu^2+/DSF共载型给药系统。利用高效液相色谱法和紫外分光光度法测定含量和包封率,激光散射粒度测定仪测定粒径及分布,透射电镜观察形态结构,应用流变仪测定相转变温度及流变学特性,并进行体外释放和细胞毒性实验。结果成功制备了Cu^2+/DSF共载型给药系统,平均粒径为198.5 nm,铜离子和DSF的包封率分别为99.7%和98.2%;相转变温度为20.2℃;对人乳腺癌细胞株MCF-7的抑制作用明显强于Cu^2+孵育条件下的DSF溶液剂。结论 Cu^2+/DSF共载型给药系统可以在体内环境下形成药物贮库,具有良好的体外抗癌效果。Objective To prepare Cu^2+/DSF co-loading drug delivery system,lipid microspheres(LMs,about 200 nm) containing copper phosphate nanoparticles(CuP/DOPA,about 20 nm) with DOPA coating and disulfiram(DSF) were embedded in the thermosensitive gel and its in vitro characteristics were investigate.Methods CuP/DOPA and DSF were co-loaded in LMs by high-pressure homogenization and then embedded in the thermosensitive gel to prepare Cu^2+/DSF co-loading drug delivery system.The system was characterized using high performance liquid chromatography(HPLC),ultraviolet spectrophotometry(UV),dynamic light scattering(DLS) and transmission electron microscopy(TEM).Sol-Gel transition temperature and rheological properties were determined via rotational rheometer.The in vitro drug release profiles and cytotoxicity of the system were also evaluated.Results The Cu^2+/DSF co-loading drug delivery system was successfully prepared,with an evenly distributed particle size of approximately 198.5 nm.The encapsulation efficiencies of the formulation were 99.7%(Cu^2+) and 98.2%(DSF),respectively.The Sol-Gel transition temperature was 20.2 ℃.The inhibitory effect of the system on MCF-7 was obviously stronger than the DSF solution under the condition of 10 μmol·L-1 Cu^2+ incubation.Conclusion The Cu^2+/DSF co-loading drug delivery system can?form a drug depot in vivo and has a good anticancer effect in vitro.

关 键 词：双硫仑 磷酸铜纳米粒 透明质酸热敏凝胶 共载型给药系统 体外释放 细胞毒性 

分 类 号：R94[医药卫生—药剂学]