甘草次酸介导pH敏感主动靶向长循环阿霉素脂质体的制备及其药物动力学

发布时间：2018-06-04 22:10

  本文选题：阿霉素 + 甘草次酸　； 参考：《沈阳药科大学学报》2015年08期

【摘要】：目的制备甘草次酸(glycyrrhetinic acid,GA)介导的pH敏感主动靶向长循环阿霉素(doxorubicin,DOX)脂质体(liposomes,LP)(GA-PEG2000-N=CH-DOXLP)并测定其在大鼠体内药物动力学参数。方法采用薄膜分散法制备甘草次酸介导pH敏感主动靶向长循环阿霉素脂质;采用阳离子交换树脂-微柱离心法测定脂质体的包封率和载药量;动态激光散射法测定脂质体的粒径、粒径分布和Zeta电位;透射电镜观察脂质体形态;透析法测定脂质体在不同pH条件下的体外释放;荧光分光光度法测定阿霉素血浆药物浓度,得到药-时曲线并计算药物动力学参数。结果甘草次酸介导的脂质体(GA-PEG2000-N=CH-DOXLP)和普通脂质体(DOXLP)的粒径分别为(135.5±2.6)nm和(105.6±4.0)nm;包封率分别为(53.8±5.8)%和(52.9±3.5)%,载药量质量分数分别为(2.35±0.16)%和(2.39±0.26)%;Zeta电位分别为-(5.19±0.73)mV和-(1.53±0.57)mV;GAPEG2000-N=CH-DOXLP的AUC(0-72)分别是DOXLP的2.33倍和DOX溶液的5.62倍。结论所制备的甘草次酸修饰的pH敏感主动靶向长循环脂质体制剂学性质稳定并能显著延长其在大鼠体内的循环时间。
[Abstract]:Objective to prepare liposome of glycyrrhetinic acid (GAA) -mediated active targeting of long-circulating doxorubicindox (doxorubicindox) liposome (GA-PEG2000-NCH-DOXLP) and determine its pharmacokinetic parameters in rats. Methods Glycyrrhetinic acid-mediated active targeting of long-circulation adriamycin lipids was prepared by thin-film dispersion method, and the entrapment efficiency and drug loading of liposomes were determined by cationic exchange resin-microcolumn centrifugation. The particle size, particle size distribution and Zeta potential of liposomes were measured by dynamic laser scattering method, the morphology of liposomes was observed by transmission electron microscope, the release of liposomes in vitro at different pH conditions was determined by dialysis, and the concentration of adriamycin in plasma was determined by fluorescence spectrophotometry. The drug-time curve was obtained and the pharmacokinetic parameters were calculated. 缁撴灉鐢樿崏娆￠吀浠嬪�肩殑鑴傝川浣�(GA-PEG2000-N=CH-DOXLP)鍜屾櫘閫氳剛璐ㄤ綋(DOXLP)鐨勭矑寰勫垎鍒�涓�(135.5卤2.6)nm鍜，

本文编号：1979015