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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。
OBJECTIVE To prepare and measure the pH-sensitive liposomes (LP) (GA-PEG2000-N = CH-DOXLP) targeting long-circulating doxorubicin (DOX) mediated by glycyrrhetinic acid (GA) Its pharmacokinetic parameters in rats. Methods The glycyrrhetinic acid-mediated pH-sensitive active long-circulating doxorubicin liposomes were prepared by membrane dispersion method. The entrapment efficiency and drug loading of liposomes were determined by cation exchange resin-micropillar centrifugation method. Dynamic laser scattering The size, particle size distribution and Zeta potential of the liposomes were determined. The morphology of the liposomes was observed by transmission electron microscopy. The in vitro release of liposomes was measured by dialysis method at different pH. The concentration of doxorubicin in plasma was determined by fluorescence spectrophotometry. Obtain drug-time curve and calculate pharmacokinetic parameters. Results The particle sizes of glycyrrhetinic acid-mediated liposomes (GA-PEG2000-N = CH-DOXLP) and common liposomes (DOXLP) were (135.5 ± 2.6) nm and (105.6 ± 4.0) nm, respectively. (53.8 ± 5.8)% and (52.9 ± 3.5)%, and the drug loading mass fraction was (2.35 ± 0.16)% and (2.39 ± 0.26)% respectively; the Zeta potentials were (5.19 ± 0.73) mV and - (1.53 ± 0.57) mV; AUC (0-72) of GAPEG2000-N = CH-DOXLP were 2.33 times that of DOXLP and 5.62 times of DOX solution, respectively. Conclusion The prepared glycyrrhetic acid modified pH-sensitive active-targeted long-circulating liposomes are stable in nature and can significantly prolong their circulation time in rats.