摘要
[目的]研究不溶于水的抗癌药物去甲斑蝥素纳米控释静脉注射制剂的制备工艺及其体内外抗肿瘤作用。[方法]以聚乳酸 聚乙醇酸共聚物(PLGA)作为基质材料 ,采用超声乳化/溶剂挥发法制备PLGA包载去甲斑蝥的纳米级微粒(NP) ,对PLGA 去甲斑蝥素 NP进行表征 ,借助扫描电镜观察微粒形态 ,通过激光光散射实验测定纳米微粒的粒径分布 ;利用高效液相色谱(HPLC)测定纳米微粒制剂的载药率及体外释放曲线 ;以MTT方法做体外杀伤癌细胞实验 ;进行两种肿瘤瘤谱在不同剂量、给药频度及制剂工艺条件下体内抑瘤实验 ;委托完成动物急性毒性试验。[结果]经电镜观察PLGA 去甲斑蝥素 NP为表面光滑的球形微粒 ,粒径分布平均值是126.4nm ,呈正态分布 ;PLGA 去甲斑蝥素 NP载药率为36.3 % ;体外释放实验提示 ,7天可释放出所载60%左右的药物 ,12天基本释放完全 ,没有显著的爆破释放 ;体内抑瘤实验表明 :控释制剂间隔给药疗效已优于未包载药物每日给药的疗效 ,量_效关系明显 ,且毒性低 ,经静脉途径试用无任何不良反应。[结论]PLGA纳米粒子可以作为抗肿瘤药物去甲斑蝥素的有效载体 ,并可成功制备其静脉注射剂型 。
To investigate the preparation techinics and anti tumor effects both in vitro & in vivo of a novel nanosphere control releasing preparation of norcantharidin(an water insoluble anti cancer drug)by intravenous injection.With polylactate poly ethanol acid copolymer(PLGA)as marix materials,we adopted ultrasound emulsification/dissolvent volatilization method to prepare PLGA enveloped norcantharidin of nano particles(NP),proceeding the appearance signs of PLGA norcantharidin NP,making use of scanning electricity microsopy to look into the morphorlogy of nanoparticles through laser optical scattering experiment and determine its diameter distribution.By means of HPLC we carry out the drug carrying coefficient(ratio)of the nanoparticles and its releasing curve in vitro.MTT method was adopted for the cancer cell bloodsheding test;Also the anti tumor effects of bi species neoplasm spetrum under different dosages,frequences of taking medicine and with various preparation techinics circumstances were observed.Observation of EM showed that PLGA norcantharidin NP nanospheres with smooth surfaces,the average diameter value was 126.4nm under normality distribution;the drug carring amount of PLGA norcantharidin NP was 36.3%.In vitro tests manifested that NP let out nearly 60% drug of its carriages in 7 days,in 12 days almost finished release totally without marked explosive discharge.As a result,experimentation in vivo indicated:nanoparticles showing apparent dosage efficacy relationship,and efficacy advantages over the unenveloped drug by interval drug delivery vs.per diem drug delivery,even with low toxicity.No mal reactions was found by introvenous injection probation.[Conclusion]Nanoparticles may serve as availability carrier of norcantharidin,anti cancer drug,and can be successesfully used in the prepation of its introvenous injection dose,so as to play more efficiency anti_tumor effects.
出处
《肿瘤学杂志》
CAS
2001年第6期321-325,共5页
Journal of Chinese Oncology
关键词
肿瘤
实验性
纳米粒子
控制释放
去甲斑蝥素
剂型
neoplasms,experimental
nanosphere
control releasing
norcantharidin
dosage forms
