柔红霉素长循环脂质体的药剂学性质及大鼠体内药代动力学研究  

STUDY ON PHARMACEUTICAL CHARACTERIZATION AND PHARMACOKINETICS OF DAUNORUBICIN LONG-CIRCULATING LIPOSOMES IN RAT

作　　者：张华[1] 齐宪荣[1] 张强[1] 

机构地区：[1]北京大学药学院药剂教研室,北京100083

出　　处：《药学学报》2002年第4期299-303,共5页Acta Pharmaceutica Sinica

摘　　要：目的　研究柔红霉素长循环脂质体的药剂学性质及大鼠体内药代动力学。方法　考察柔红霉素长循环脂质体的形态和粒径分布、包封率和加速实验稳定性 ;建立脂质体中柔红霉素含量测定的可见分光光度法和HPLC方法 ;考察脂质体在Hepes缓冲液 (pH 7 5 )和大鼠血清中的体外释放行为。考察脂质体在大鼠体内的药代动力学行为。结果　制备的柔红霉素长循环脂质体包封率高 ( >85 % )、稳定性好 ,平均粒径为 5 6 3nm ,体外释放慢 ;长循环脂质体的T1 2 α和AUC分别是注射剂的 17 6和 96倍。结论　制备的长循环脂质体包封率较高 ,药剂学性质稳定 ,在大鼠体内的药代动力学参数优于注射剂 。AIM To study the pharmaceutical characterization and pharmacokinetics of long circulating liposomes containing daunorubicin. METHODS The morphology of daunorubicin long circulating liposome was surveyed under the transmission electron microscope. The size of daunorubicin long circulating liposomes was determined by laser scatter method. The entrapment efficiency and accelerative experiment stability of the daunorubicin long circulating liposomes were examined. Visible spectrophotometry and the HPLC method were established for determination of the daunorubicin in the long circulating liposomes. The percent release of daunorubicin from long circulating liposomes in HBS (pH 7 5) and rat serum at 37℃ were examined. The pharmacokinetics in rats were studied. RESULTS The high entrapment efficiency (>85%) and stabilized long circulating liposomes could be achieved. The drug was slowly released from the daunorubicin long circulating liposomes. The drug released from liposomes was less than 10% in 24 h. The T 1/2 α and AUC of long circulating liposome were higher than those in injections. CONCLUSION The long circulating liposomes prepared by us have high encapsulation efficiency and the pharmaceutical characterization showed good stability, they can be used for clinical purpose.

关 键 词：长循环脂质体 柔红霉素 包封率 体外释放 药代动力学 

分 类 号：R978.15[医药卫生—药品] R944.9[医药卫生—药学]