聚(2-乙基-2-噁唑啉)修饰姜黄素脂质体的制备及评价  

Preparation, characterization and in vitro evaluation of poly（2-ethyl-2-oxazoline） modified curcumin liposomes

作　　者：何薪宇 吕静[1] 苏红[1] 徐缓[1] HE Xin-yu LV Jing SU Hong XU Huan(College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China)

机构地区：[1]辽宁师范大学化学化工学院

出　　处：《中国生化药物杂志》2017年第6期16-19,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81102394);辽宁省自然科学基金(201701207);辽宁师范大学本科生实验室开放项目(cx20160112);辽宁省大学生创新创业训练计划项目(201610165000015)

摘　　要：目的 制备姜黄素脂质体（Curcumin liposome,Cur-L）,利用聚（2-乙基-2-噁唑啉）-胆固醇氯甲酸酯（poly（2-ethyl-oxazoline）-cholesteryl methyl carbonate,PEOZ-CHMC）对其进行修饰,考察其相关性质.方法 采用薄膜分散法制备Cur-L,以包封率和粒径为评价指标,综合加权评分法筛选Cur-L的最优处方.利用PEOZ-CHMC修饰Cur-L得到PEOZ-Cur-L,利用葡聚糖凝胶-微柱离心法测定其包封率,采用激光粒度测定仪和透射电镜考察其粒径和形态,透析法考察2种Cur-L的体外释放情况,MTT法考察2种Cur-L的细胞抑制作用.结果 Cur-L最优处方为：药脂比1.56（w/w）,大豆磷脂与胆固醇的质量比5.1（w/w）,PBS缓冲液的pH值为7.4,Cur-L的包封率为（75.05±0.64）%,经PEOZ修饰脂质体的包封率没有显著改变.透射电镜显示PEOZ-Cur-L具有明显的脂质双分子层结构,PEOZ-Cur-L的平均粒径为84.89nm.体外释放实验表明,在pH 7.4的条件下24h内Cur-L的累积释放率大于70%,PEOZ-Cur-L的累积释放率小于25%.细胞毒性实验显示PEOZ-Cur-L对HCT116人结肠癌细胞具有更好的抑制作用.结论 优选的Cur-L的处方和制备工艺合理可行,PEOZ可赋予脂质体良好的稳定性,并不妨碍其细胞抑制作用.Objective To prepare Curcumin liposome （Cur-L） and poly（2-ethyl-oxazoline）-cholesteryl methyl carbonate （PEOz-CHMC） was used to modified Cur-L and to evaluate their associated properties in vitro.MethodsEncapsulation efficiency and particle size were taken as evaluation indicators to optimize the formulation and preparation conditions of Cur-L by orthogonal test.The EE, particle size and shape of the liposomes were determined by sephadex G-50 mini-column centrifugation method, ZLS dynamic light scattering instrument and transmission electron microscopy （TEM）, respectively.The release of the liposome in vitro was detected by The dialysis method.MTT assay was used to determine the cell inhibition of two Cur-L.ResultsThe optimized preparing method of Cur-L is as following： 1.56（w/w） as drug-lipid ratio, 5.1（w/w） as the ratio of mass of phosphatide and cholesterol, 7.4 as the pH of PBS buffer.The EE of Cur-L was （75.05±0.64）%, while the modification of PEOZ hasno influences on EE.Through TEM, PEOZ-Cur-L has aobviouslipid bilayer structure.The average particle diameter of PEOZ-Cur-L was 84.89 nm.In vitro release experiments showed that in 24h, the accumulative release rate of Cur-L is more than 70% with pH 7.4, while that of PEOZ-Cur-L was less than 25%.The cytotoxicity experiment showed that PEOZ-Cur-L can inhibit HCT116 Human colon cancer cells more effectively.ConclusionThe optimized preparing method of Cur-L is reasonable.PEOZ can provide stability to liposomes well and does not hamper its inhibitive effects.

关 键 词：脂质体 姜黄素 聚(2-乙基-2-噁唑啉) 稳定性 

分 类 号：R285[医药卫生—中药学]