摘要
[目的]制备HRZ三联抗痨药/TGF-β1 siRNA纳米脂质体,对其理化性质、药代动力学等进行表征分析。[方法]用反相蒸发法制备PEG2000修饰的异烟肼(H)、利福平(R)及吡嗪酰胺(Z)三联抗痨药脂质体,包裹TGF-β1 siRNA。测定脂质体粒径、电位、包封率并进行电镜观察。[结果]成功制备HRZ三联抗痨药阳离子脂质体,Zeta电位值(28.13±2.4) mV,异烟肼、利福平及吡嗪酰胺包封率分别为90%、88%、37%;随着阳离子脂质体用量的增加,siRNA包裹效果越好,Zeta电位值逐渐由负变正;动态光散射技术(DLS)及透射电镜(TEM)显示,HRZ三联抗痨药/TGF-β1 siRNA纳米脂质体呈球形,大小均匀,粒径为(152.69±59.47) nm。[结论]成功构建HRZ三联抗痨药/TGF-β1 siRNA纳米脂质体,为后续进一步进行体外细胞毒性、靶向TGF-β1基因沉默效应及结核分枝杆菌(MTB)感染宿主细胞体内、体外抗结核实验提供了研究基础。
[Objective] To prepare HRZ triple antituberculosis drugs/TGF-β1 siRNA nanoliposomes and explore their physicochemical properties and pharmacokinetics. [Methods] PEG2000-modified isoniazid(H), rifampicin(R) and pyrazinamide(Z) triple antituberculosis drug liposomes were prepared by reversed phase evaporation and then encapsulated by TGF-β1 siRNA. The liposomes were measured for particle size, potential, and encapsulation efficiency, as well as observed by electron microscopy. [Results] The HRZ triple antituberculosis cationic liposome was successfully prepared with zeta potential value of28.13±2.4 mV. The entrapment efficiencies of isoniazid, rifampicin and pyrazinamide were 90%, 88% and 37% respectively.With increasing amounts of plastids, the effect of siRNA encapsulation was improved, and the zeta potential gradually changed from negative to positive. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) showed that HRZ triple antituberculosis drugs/TGF-β1 siRNA nanoliposomes were spherical and uniform in size with a particle size of(152.69 ±59.47) nm. [Conclusion] We successfully constructed HRZ triple antituberculosis drugs/TGF-β1 siRNA nanoliposomes,which provide the basis for further experiments of in vitro cytotoxicity, targeting silencing of TGF-β1 gene and anti-tuberculosis tests of Mycobacterium tuberculosis(MTB) infected host cells in vitro and in vivo.
作者
牛宁奎
师志云
施建党
王自立
杨宗强
马文鑫
耿广起
丁惠强
NIU Ning-kui;SHI Zhi-yun;SHI Jian-dang;WANG Zi-li;YANG Zong-qiang;MA Wen-xin;Geng Guang-qi;DING Hui-qiang(General Hospital of Ningxia Medical University,Yinchuan 750004,China)
出处
《中国矫形外科杂志》
CAS
CSCD
北大核心
2018年第23期2177-2182,共6页
Orthopedic Journal of China
基金
国家自然科学基金项目(编号:81501903
81860395)
宁夏医科大学青年骨干人才培育计划项目
宁夏高等学校一流学科建设(宁夏医科大学国内一流建设学科临床医学)资金项目(编号:NXYLXK2017A05)
作者简介
牛宁奎,医学博士,副主任医师,研究方向:脊柱感染及骨肿瘤,(电话)13629593280,(电子信箱)niuningkui@163.com;通信作者:丁惠强,(电话)0951-6743242,13709577721,(电子信箱)nyfyguke@126.com.
