米托蒽醌隐形阳离子脂质体的制备及体内外抗肿瘤活性  

Preparation and antitumor activity of mitoxantrone-loaded stealth cationic liposomes

作　　者：胡廷婷[1] 杨成莉 曹华[1] 张利静 贺英菊[1] 郑瑀 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]华西医院生物治疗国家重点实验室/生物治疗协同创新中心,四川成都610041

出　　处：《中国医院药学杂志》2015年第11期1003-1007,共5页Chinese Journal of Hospital Pharmacy

基　　金：第五十四批中国博士后科学基金会资金(编号:2013M542421);第7批中国博士后科学基金会资金

摘　　要：目的:制备米托蒽醌隐形阳离子脂质体(YM),并研究其制剂学性质及体内外抗肿瘤作用。方法:膜材料中引入2-二油酰基羟丙基-3-N,N,N-三甲铵氯(DOTAP)和聚乙二醇2000-二硬脂酰磷脂乙醇胺(DSPE-PEG2000)分别作为阳性和隐形膜材,采用硫酸铵梯度法制备YM,并以泄漏率为指标,考察其稳定性;高内涵扫描仪考察2 h时其在B16F10细胞中的摄取情况;MTT法测定其对B16F10细胞的增殖影响;B16F10皮下移植瘤模型研究其体内抗肿瘤作用。结果:YM的粒径和Zeta电位分别为(118.2±4.6)nm和(31.6±4.9)m V;载药量和包封率分别为(6.5±0.2)%和(96.2±1.8)%;血清中48 h累积泄漏率<30%,稳定性良好;YM的细胞摄取量是普通长循环脂质体(CM)的10倍,IC50与CM相比显著降低(P<0.05),体内抑瘤率为58.8%,显著高于CM组的42.7%。结论:YM稳定性良好,具有较好的体内外抗肿瘤活性。OBJECTIVE To investigate the preparing method and antitumor activity of mitoxantrone-loaded stealth cationic liposomes( YM). METHODS YM were prepared by using ammonium sulfate gradients method composed of dioleoyl-3-trimethylammonium-propane( DOTAP) and DSPE-PEG2000. Leakage profiles were used as index to study liposomal stability in FBS. Cell uptake characteristics by B10F10 cells in vitro were determined by high content screening( HCS),the antiproliferative effects on B10F10 cells were evaluated by MTT assay,and then in vivo antitumor activities were evaluated by subcutaneously transplanting tumor models of B10F10 cells. RESULTS The mean particle size and zeta potential of YM were( 118. 2 ± 4. 6) nm and( 31. 6 ± 4. 9) m V,respectively,with a high encapsulation efficiency of( 96. 2 ± 1. 8) %. The accumulative leakage of YM against FBS was less than 25% within 48 h. B16F10 cellular uptake of YM was 10 times as many as the ordinary long-circulating liposomes( CM),IC50 of YM in B16F10 cells were significantly lower than CM( P < 0. 05),and in vivo inhibitory rate on tumor of YM was 58. 8%,which was remarkably higher than that of CM( 42. 7%). CONCLUSION YMs are in stable in FBS and have better antitumor effects compared with CM.

关 键 词：米托蒽醌 隐形阳离子脂质体 抗肿瘤 药效学 

分 类 号：R944[医药卫生—药剂学]