摘要
制备了DPH荧光脂质体,选用10种药理活性较好的中药单体,测定了这些中药单体进入荧光脂质体后引起的荧光衰减百分率,评估中药单体的细胞膜通透性。采用大鼠在体肠单向灌流实验测定了中药单体的小肠有效透皮系数(Peff),与中药单体引起的脂质体荧光衰减数据对比,两者相关性良好,从而证明荧光脂质体模型可以应用来预测中药单体的被动吸收。用DPH标记红细胞膜,测定了以上10种中药单体对荧光标记的红细胞膜的荧光衰减百分率,发现荧光脂质体与红细胞膜相关性良好,荧光脂质体模型的确可以一定程度上替代制备繁琐的红细胞膜,用来研究中药单体在真实细胞膜中的通透性。综合而言,荧光脂质体模型简单易行、重现性好、所需样品量少,适合于中药早期研究的高通量筛选。
Fluorescent 1,6-diphenyl-1,3,5-hexatriene （DPH） liposomes were prepared herein and used to predict the membrane permeability of 10 kinds of natural products. Fluorescence quenching percentages of 10 kinds of natural products on the DPH liposomes were thus determined and their effective intestinal permeability coefficient （Pert） was carried out by rat single-pass intestinal perfusion experiments. The data show that a good linearity （r = 0. 85 ） was observed between the fluorescence quenching percentage and Peff Furthermore, the erythrocyte membrane was labeled by DPH, and then the erythrocyte membrane fluorescence quenching percentage caused by 10 kinds of natural products was determined. After comparing the liposome and erythrocyte membrane fluorescence quenching percentages, it was also found that a good linearity （ r = 0. 93 ） was shown between these two methods. Overall, fluorescent liposomes could be simply and sensitively employed to predict passive transport of natural products and permeability in erythrocyte membrane, and fluorescent liposomes were thus an attractive alternative to current rat intestinal experiments and erythrocyte membrane model. This protocol will be quite promising in predicting drug passive absorption during lead compound selection and drug development.
出处
《分析化学》
SCIE
EI
CAS
CSCD
北大核心
2007年第12期1696-1700,共5页
Chinese Journal of Analytical Chemistry
基金
国家自然科学基金资助(No.90409017
20675019)
关键词
荧光脂质体
中药单体
细胞膜通透性
大鼠小肠吸收实验
红细胞膜
Fluorescent liposomes, natural products, membrane permeability, rat single-pass intestinal perfusion experiments, erythrocyte membrane
