薯蓣皂苷元衍生物双药自组装纳米给药系统的构建及质量评价  

Preparation and evaluation of the dual-drug self-assembled nanodrug delivery systems of diosgenin derivative

作　　者：李金鑫 许杜娟 刘萌芽 史礼君 蔡邦荣 刘改枝[1] LI Jin-xin;XU Du-juan;LIU Meng-ya;SHI Li-jun;CAI Bang-rong;LIU Gai-zhi(School of Pharmacy,Henan University of Chinese Medicine,Henan Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,河南郑州450046

出　　处：《中国医院药学杂志》2022年第18期1857-1861,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家青年基金项目(编号:81803740);河南省高等学校重点科研项目(编号:22A350015);中国博士后科学基金面上项目(编号:2020M682311)。

摘　　要：目的:构建药辅同源双药自组装纳米给药系统,并对其进行质量评价。方法:以薯蓣皂苷元(diosgenin, DG)为原料,设计、合成具有两亲性的DG衍生物(DGG),运用~1H-NMR、C-NMR和HR-MS对其结构进行确证;稳态荧光法测定临界聚集浓度;将DGG和二十二碳六烯酸(docosahexaenoic acid, DHA)等比混合,采用纳米沉淀法制备DGG/DHA(DD NPs)双药自组装纳米给药系统,以粒径和PDI值为指标对处方进行单因素考查并优化,通过透射电镜、激光粒径仪对纳米粒的形态、粒径及分布进行表征,并对其稳定性、包封率、载药量和溶血性进行评价。结果:DD NPs双药自组装纳米粒的平均粒径为(164.1±3.9) nm,载药量为(63.24±0.39)%,储存稳定性良好;实验表明,DD NPs在酸性条件下有一定的溶血性。结论:DD NPs形成稳定性良好、粒径小、载药量高的类球状双药纳米给药系统,为DG和DHA协同抗肿瘤研究和应用奠定了基础。OBJECTIVE The dual-drug self-assembled nanodrug delivery systems was prepared, and its quality was evaluated.METHODS Taking diosgenin(DG)as raw material, an amphiphilic diosgenin derivative(DGG)was designed and synthesized.The structure of DGG was confirmed by ~1H-NMR,C-NMR and HR-MS spectra.The critical aggregation concentration of DGG was measured by steady-state fluorescence method.DGG and docosahexaenoic acid(DHA)were mixed in equal proportions, and the DGG/DHA dual-drug self-assembled nanoparticle(DD NPs)was prepared by the nanoprecipitation method.The preparation method of the optimized prescription was investigated under the indication of particle size and PDI.The particle size and morphology of DD NPs were characterized by transmission electron microscopy(TEM)and dynamic light scattering method(DLS).The properties of DD NPs, including stability, drug encapsulation, loading capacity and hemolysis were evaluated.RESULTS The mean particle size of DD NPs was(164±3.9) nm, and the drug loading capacity was(63.24±0.39)%.The nanoparticle also showed high storage stability.The hemolysis results showed that DD NPs had some hemolysis under acidic conditions(pH=5.5).CONCLUSION The spherical dual-drug nanodrug delivery systems(DD NPs)with stability, the smaller size and higher drug loading successfully prepared in this study.It provided an effective strategy potential for combination therapy using DG and DHA in the treatment of diverse tumors.

关 键 词：薯蓣皂苷元 二十二碳六烯酸 自组装 纳米给药系统 

分 类 号：R944.9[医药卫生—药剂学]