去甲斑蝥素纳米胶束的制备及抑瘤作用研究  

Preparation of Norcantharidin Nano-micelle and Study on Its Antitumor Effect

作　　者：王琳[1,2] 陆丹玉[1] 方晨[3] 

机构地区：[1]苏州卫生职业技术学院药学院,江苏苏州215009 [2]苏州大学医学部药学院,江苏苏州215213 [3]香港浸会大学中医药学院

出　　处：《中国药房》2017年第19期2680-2684,共5页China Pharmacy

基　　金：江苏省卫生厅科技项目(No.JZ201402)

摘　　要：目的:制备去甲斑蝥素纳米胶束,并研究其抑瘤作用。方法:采用三嵌段共聚物二硬脂酰磷脂酰乙醇胺-聚乙二醇-马来酰亚胺在水中自组装形成去甲斑蝥素纳米胶束。观察所制纳米胶束形态,考察其载药率、包封率、粒径和Zeta电位。通过MTT法考察阴性对照组(磷酸盐缓冲液)、载体组(空白纳米胶束)、阳性对照组(去甲斑蝥素原料药,5~320μg/m L)和去甲斑蝥素纳米胶束组(以去甲斑蝥素计,5~320μg/m L)人肺癌A549细胞在作用不同时间(24、48、72 h)后的细胞生存率。将荷瘤裸鼠随机分为空白对照组、去甲斑蝥素注射液组(1 mg/kg)和去甲斑蝥素纳米胶束低、高剂量组(0.5、1 mg/kg),每组6只,每天尾iv相应药物1次,连续8周;每周测量肿瘤的大小,给药结束后第2天检测瘤质量。结果:去甲斑蝥素纳米胶束呈圆球状,载药率为(2.82±0.05)%,包封率为(83.67±1.78)%,粒径为(138.6±45.8)nm,Zeta电位为-(12.75±0.34)m V(n=6);载体组A549细胞生存率无明显变化,阳性对照组和去甲斑蝥素纳米胶束组A549细胞生存率明显降低,与浓度和时间呈正相关,且去甲斑蝥素纳米胶束组细胞生存率降低程度较阳性对照组更明显(P<0.01)。与空白对照组比较,3个给药组裸鼠的瘤质量均减小(P<0.05),其中去甲斑蝥素纳米胶束高剂量组减小程度较去甲斑蝥素注射液组更明显(P<0.05)。结论:成功制得去甲斑蝥素纳米胶束,其对A549细胞具有较好的体内外抑瘤作用。OBJECTIVE：To prepare the norcantharidin（NCTD） nano-micelle and study its antitumor effect. METHODS：NCTD nano-micelle was self-formed in water using Triblock copolymers distearyl phosphatidylethanolamine-polyethylene glycol-maleimide;its shape was observed,the drug-loading rate,entrapment efficiency,particle size,Zeta potential were investigated. MTT was used to investigate the cell survival rate of human lung cancer A549 cells in negative control group（Phosphate buffer solution）,carrier group（blank nano-micelle）,positive control group（NCTD APIs,5-320 μg/m L） and NCTD nano-micelle group（NCTD,5-320 μg/m L）after acting different time（24,48,72 h）. Tumor nude mice were randomly divided into blank control group,NCTD injection group（1 mg/kg）,NCTD low-dose,high-dose groups（0.5,1 mg/kg）,6 in each group. All mice were intravenously injected relevant medicines in tail,once a day,for 8 weeks. Tumor size was measured every week,and tumor quality was detected after the second day of finishing administration. RESULTS：NCTD nano-micelle was round,drug-loading rate was（2.82±0.05）%,entrapment efficiency was（83.67±1.78）%,particle size was（138.6±45.8）nm,Zeta potential was-（12.75±0.34）m V（n=6）. Cell survival rate of A549 cells in carrier group had no obvious changes,and was obviously decreased in positive control group and NCTD nano-micelle group,which was positively correlated with concentration and time. And the decrease degree of cell survival rate in NCTD nano-micelle group was stronger than positive control group（P〈0.01）. Compared with blank control group,the tumor quality of mice in 3 administration groups was reduced（P〈0.05）,the reduction degree in NCTD nanomicelle high-dose group was stronger than NCTD nano-micelle injection group（P〈0.05）. CONCLUSIONS：NCTD nano-micelle is successfully prepared,which has good in vitro and in vitro anti-tumor effect on A549 cells.

关 键 词：二硬脂酰磷脂酰乙醇胺-聚乙二醇-马来酰亚胺 去甲斑蝥素 纳米胶束 抑瘤作用 

分 类 号：R943[医药卫生—药剂学] R361.3[医药卫生—药学]