摘要
目的制备冬凌草甲素脂质体,延长冬凌草甲素体内循环时间,提高生物利用度。方法采用薄膜分散法制备冬凌草甲素脂质体,测定其粒径、多分散指数、zeta电位及包封率。采用交叉实验法,以大鼠为模型动物分别经尾静脉单次注射(20 mg/kg)给予冬凌草甲素溶液和冬凌草甲素脂质体,利用超高效液相色谱法测定不同时间点的血浆冬凌草甲素质量浓度,PKSolver软件计算药动学参数。结果制备得到的冬凌草甲素脂质体平均粒径为142 nm,多分散指数为0.246,zeta电位-24.3 mV,包封率84.2%。大鼠单次尾静脉注射冬凌草甲素溶液及脂质体,模型拟合均符合二室模型。冬凌草甲素溶液和冬凌草甲素脂质体在大鼠体内的消除半衰期分别为(3.14±0.61)h和(14.38±3.69)h,平均驻留时间分别为(3.57±0.89)h和(19.30±5.04)h,血药浓度曲线下面积分别为(2.36±0.27)μg·h/ml和(9.51±1.11)μg·h/ml,差异均具有统计学意义(P<0.05)。结论本研究制备的冬凌草甲素脂质体工艺简单可行,脂质体制剂通过延长半衰期和平均驻留时间,延长冬凌草甲素在大鼠体内的循环时间,增加药-时曲线下面积,从而提高生物利用度。
Objective To prepare oridonin liposomes with long blood circulation time and high bioavailability.Methods Oridonin liposomes were prepared by thin film dispersion method,and the particle size,the polydispersity index,the zeta potential,and the encapsulation efficiency were determined.Using a cross-over assay,the rats were injected with oridonin solution and oridonin liposomes at a dose of 20 mg/kg via tail vein,respectively.Then the content of oridonin in rat plasma was determined by ultra-high performance liquid chromatography at different time points.The pharmacokinetic parameters were calculated by PKSolver software.Results The prepared oridonin liposomes had an average particle size of 142 nm,a polydispersity index of 0.246,a zeta potential of-24.3 mV,and an encapsulation efficiency of 84.2%.The models of intravenous injection of oridonin liposomes and oridonin solution fitted with two-compartment model.The elimination half-life was(3.14±0.61)h and(14.38±3.69)h for oridonin solution and oridonin liposomes,respectively,the mean residence time was(3.57±0.89)h and(19.30±5.04)h,and the area under the curve was(2.36±0.17)μg·h/ml and(9.51±1.11)μg·h/ml,respectively,and there was statistically significant difference in the above indexes(P<0.05).Conclusion The preparation technology of oridonin liposome in this study is simple and feasible.The oridonin liposomes can prolong the half-life and the mean residence time,prolong the circulation time in rats,and increase the area under the curve,thus improving the bioavailability.
作者
常路晗
王银月
崔伊曼
王振
吴志刚
王金
CHANG Luhan;WANG Yinyue;CUI Yiman;WANG Zhen;WU Zhigang;WANG Jin(Department of Pharmaceutics,Hebei North University,Zhangjiakou 075000,China;Hebei Key Laboratory of Neuropharmacology)
出处
《山西医科大学学报》
CAS
2023年第1期119-124,共6页
Journal of Shanxi Medical University
基金
国家级大学生创新创业训练计划项目(202110092007X)
张家口市重点研发计划项目(2221184D)。
关键词
冬凌草甲素
脂质体
药动学
超高效液相色谱法
oridonin
liposomes
pharmacokinetics
ultra-high performance liquid chromatography
作者简介
常路晗,男,2001-03生,在读本科,E-mail:136547395@qq.com;通讯作者:王金,E-mail:wangjinzym@163.com。
