Song Haifeng, Zhang Jin, Han Zhikai, Zhang Xueyan, Li Zheng, Zhang Lisheng, Fu Ming, Lin Chen, Ma Jie
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, PUMC, Beijing, 100021, China.
Cancer Chemother Pharmacol. 2006 May;57(5):591-8. doi: 10.1007/s00280-005-0076-6. Epub 2005 Aug 30.
Pegylated liposomes have been studied for nearly two decades. However, fewer pharmacological studies about its application in daunorubicin (DNR) than those in doxorubicin have been reported. In order to conduct a complete pharmacokinetic study, radiolabeled DNR was encapsulated in pegylated liposomes. Its in vitro drug release kinetics was determined to be in a slow manner, which was reflected in its cytotoxic effect on four cell lines. The lethal dose, plasma pharmacokinetics as well as tissue distribution of the formulation were evaluated in comparison with free DNR. The results revealed that liposomal daunorubicin significantly reduced the toxicity of the drug, with a half lethal dose of 29.35 mg/kg, compared with 5.45 mg/kg for free drug. Pharmacokinetic study of liposomal DNR demonstrated a slower clearance rate, an elevated area under the concentration-time curve, as well as increased half-lives compared to free drug. In addition, an altered tissue distribution of liposomal DNR was observed, with lower cardiac accumulation. Taken together, pegylated liposome-loaded DNR may be a promising anticancer drug and worth further therapeutic study.
聚乙二醇化脂质体已被研究了近二十年。然而，与阿霉素相比，关于其在柔红霉素（DNR）中的应用的药理学研究报道较少。为了进行完整的药代动力学研究，将放射性标记的DNR包裹在聚乙二醇化脂质体中。其体外药物释放动力学被确定为缓慢释放，这反映在其对四种细胞系的细胞毒性作用上。与游离DNR相比，评估了该制剂的致死剂量、血浆药代动力学以及组织分布。结果显示，脂质体柔红霉素显著降低了药物的毒性，半数致死剂量为29.35mg/kg，而游离药物为5.45mg/kg。脂质体DNR的药代动力学研究表明，与游离药物相比，其清除率较慢，浓度-时间曲线下面积增加，半衰期延长。此外，观察到脂质体DNR的组织分布发生改变，心脏蓄积较低。综上所述，聚乙二醇化脂质体负载的DNR可能是一种有前途的抗癌药物，值得进一步进行治疗研究。
