摘要
目的 探讨聚乙二醇（PEG）修饰的柔红霉素（DNR）脂质体（PL-DNR）治疗白血病的疗效及其毒副作用.方法 采用薄层水化法和主动载药法制备PL-DNR,测定理化指标,进行体外细胞增殖抑制实验,分析PL-DNR对白血病细胞的杀伤作用.利用L1210荷瘤鼠白血病模型评价PL-DNR的体内抑瘤效果.采用原位末端转移酶标记法分析药物对小鼠的心肌毒性.结果 PL-DNR粒径大小为（110±10）nm,包封率为94.21％.体外增殖抑制实验显示,PL-DNR的抑瘤能力随实验时间延长逐渐增强.体内药效学实验显示,PL-DNR抑瘤效果明显,PL-DNR组和DNR组的肿瘤体积分别为（433.71±234.77） mm3和（1 293.77±381.26） mm3,差异有统计学意义（P＜0.05）.PL-DNR组和DNR组的瘤重分别为（0.66 ±0.29）g和（1.25 ±0.43）g,差异有统计学意义（P＜0.05）.心肌毒性实验显示,PL-DNR组和DNR组小鼠的心肌组织中位凋亡细胞阳性指数分别为13.83％和42.67％（P＜0.05）.结论 与柔红霉素相比,PEG修饰的柔红霉素脂质体可提高原药对白血病的治疗效果,同时降低对心肌的毒副作用.
Objective To explore the antitumor effect and toxicity of pegylated liposomal daunorubicin （PL-DNR） on leukemia.Methods PL-DNR was prepared by dry lipid hydration and remote loading,and its physicochemical indexes were analyzed.The inhibiting effect of PL-DNR on leukemia cells was observed in terms of in vitro cytotoxicity experiment.The therapeutic effect in vivo was assessed by tumor inhibition in leukemia L1210-bearing mice.Apoptosis in cardiomyocytes was detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method （TUNEL staining）.Results The average diameter of PL-DNR was （110 ± 10） nm and the encapsulation efficiency was 94.21％.The in vitro cytotoxicity experiment showed that the inhibiting ability of PL-DNR in the treatment groups was continuously enhanced as the experiment proceeded.The in vivo pharmacodynamic experiment also indicated obvious tumor-inhibiting effect of PL-DNR.At the end of the experiment,the tumor volume of the PL-DNR group was （433.71 ± 234.77） mm3,significantly smaller than that of （1 293.77 ± 381.26） mm3 in the DNR group （P ＜ 0.05）.Moreover,the tumor weight of the PL-DNR group was （0.66 ± 0.29） g and that of the DNR group was （1.25 ± 0.43） g （P ＜ 0.05）.The myocardial toxicity experiment showed that the median apoptosis index of cardiomyocytes in the PL-DNR group was 13.83％,significantly lower than that of 42.67％ in the DNR group （P ＜0.05）,indicating a lower toxicity of PL-DNR to the myocardium.Conclusion Compared with the free DNR,PL-DNR can improve the therapeutic effect on leukemia and reduce the cardiotoxicity.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2014年第10期746-750,共5页
Chinese Journal of Oncology
