木犀草素固体脂质纳米粒的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of luteolin solid lipid nanoparticles

作　　者：杨娟[1] 尚曙玉[1] 贾安[1] 郭锐税 冯永豪 YANG Juan;SHANG Shu-yu;JIA An;GUO Rui-shui;FENG Yong-hao(College of Medicine,Huanghe Science and Technology College,Zhengzhou 450006,China;Shanghai Leiyunshang Pharmaceutical Co.,Ltd.,Shanghai 201401,China)

机构地区：[1]黄河科技学院医学院,河南郑州450006 [2]上海雷允上药业有限公司,上海201401

出　　处：《中成药》2021年第9期2281-2286,共6页Chinese Traditional Patent Medicine

基　　金：2017年河南省科技厅科技发展项目(172102310528);2017年河南省高等学校重点研究项目(18B360010)。

摘　　要：目的制备木犀草素固体脂质纳米粒,并评价其体内药动学。方法乳化蒸发-低温固化法制备固体脂质纳米粒后,考察其形态、包封率、载药量、粒径、Zeta电位、体外释药。12只大鼠随机分为2组,分别灌胃给予木犀草素及其固体脂质纳米粒冻干粉的0.5%CMC-Na混悬液(10 mg/kg),于0.15、0.5、0.75、1、1.5、2、4、6、8、12 h采血,HPLC法测定木犀草素血药浓度,计算主要药动学参数。结果所得固体脂质纳米粒呈类球形或球形,平均包封率为85.24%,载药量为5.24%,粒径为176.35 nm,Zeta电位为-33.8 mV,24 h累积溶出度为71.5%,体外释药符合Weibull模型(R2=0.9792)。与原料药比较,固体脂质纳米粒t_(max)延长(P<0.01),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度提高至2.28倍。结论固体脂质纳米粒可促进木犀草素口服吸收,提高其生物利用度。AIM To prepare luteolin solid lipid nanoparticles and to evaluate their in vivo pharmacokinetics.METHODS Emulsification evaporation-low temperature solidification method was employed to prepare solid lipid nanoparticles,after which their morphology,encapsulation efficiency,drug loading,particle size,Zeta potential and in vitro drug release were investigated.Twelve rats were randomly assigned into two groups and given intragastric administration of the 0.5%CMC-Na suspensions(10 mg/kg)of luteolin and its solid lipid nanoparticles’lyophilized powder,respectively,after which blood collection was made at 0.15,0.5,0.75,1,1.5,2,4,6,8,12 h,HPLC was adopted in the plasma concentration determination of luteolin,and main pharmacokinetic parameters were calculated.RESULTS The obtained spherical-like or spherical solid lipid nanoparticles demonstrated the average encapsulation efficiency,drug loading,particle size,Zeta potential and accumulative dissolution rate within 24 h were 85.24%,5.24%,176.35 nm,-33.8 mV and 71.5%,respectively,and the in vitro drug release accorded with Weibull model(R^(2)=0.9792).Compared with the raw medicine,the solid lipid nanoparticles displayed prolonged t_(max)(P<0.01)and increased C_(max),AUC_(0-t) and AUC_(0-∞)(P<0.01),and the relative bioavailability was enhanced to 2.28 times.CONCLUSION Solid lipid nanoparticles can improve the oral absorption of luteolin and elevate its bioavailability.

关 键 词：木犀草素 固体脂质纳米粒 制备 体内药动学 乳化蒸发-低温固化法 HPLC 

分 类 号：R944[医药卫生—药剂学]