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Epirubicin-encapsulated long-circulating thermosensitive liposome improves pharmacokinetics and antitumor therapeutic efficacy in animals

文献类型： 外文期刊

作者： Wu, Yan 1 ; Yang, Yuan 2 ; Zhang, Fu-Cheng 1 ; Wu, Cheng 3 ; Lue, Wan-Liang 4 ; Mei, Xing-Guo 5 ;

作者机构： 1.Gen Hosp Air Force, Dept Pharm, Beijing, Peoples R China

2.Beijing Acad Agr & Forestry Sci, Inst Forestry & Pomol, Beijing, Peoples R China

3.Gen Hosp Second Artillery, Dept Pharm, Beijing, Peoples R China

4.Peking Univ, Sch Pharm, Beijing 100871, Peoples R China

5.Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China

关键词： Thermosensitive;liposome;pharmacokinetics;epirubicin hydrochloride;antitumor

期刊名称：JOURNAL OF LIPOSOME RESEARCH （ 影响因子：3.648； 五年影响因子：3.649 ）

ISSN： 0898-2104

年卷期： 2011 年 21 卷 3 期

页码：

收录情况： SCI

摘要： In the present work, a long-circulating epirubicin hydrochloride (EPI)-containing thermosensitive liposome aiming at antitumor therapy, DPPC/MSPC/DSPG/DSPE-mPEG(2000) (EPI-LTSL), was developed and evaluated. Nonthermosensitive and traditional liposomes, HSPC/cholesterol/DSPG/DSPE-mPEG(2000) (EPI-NTSL) and HSPC/cholesterol (EPI-LIP), were also prepared at the same time for comparison. Temperature-dependent EPI release from loaded liposomes in vitro was characterized by the fluorescence method. Different liposome preparations were administered in rats by intravenous injection at the same dosage of 12 mg.kg(-1). EPI and internal standard daunorubicin hydrochloride (DAU) were analyzed by high-performance liquid chromatography and verified by LC tandem mass spectrometry. In the pharmacodynamics study, the EPI-LTSL was combined with local hyperthermia for target-specific delivery to the anesthetized and tumor-bearing mice. According to the in vitro results, more than 90% of loaded EPI was released from MSPC-containing liposome (EPI-LTSL) within 4 minutes at 43 degrees C, while at 37 degrees C, less than 5% was released beyond 60 minutes. However, less than 5% of drug was released at 43 degrees C for the other two liposomes without MSPC (EPI-NTSL and EPI-LIP). The results of the pharmacokinetics study in rats showed that not only the circulation time of EPI was prolonged significantly, but also the concentration in vivo was promoted for EPI-LTSL, compared to EPI-NTSL and EPI-solution. The mean tumor inhibitory rate for EPI-LTSL, EPI-NTSL, and EPI-solution were 61.1, 39.6, and 43.1%, respectively.

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