多西紫杉醇-海豹油纳米结构脂质载体的抗肿瘤活性评价

发布时间：2018-03-28 15:44

本文选题：多西紫杉醇　切入点：纳米结构脂质载体　出处：《首都医科大学学报》2015年02期

【摘要】：目的探讨多西紫杉醇(docetaxel,DTX)海豹油脂质体的抗肿瘤活性以及与脂肪乳的比较。方法采用正交试验设计法筛选处方,通过高压乳匀法制备多西紫杉醇海豹油脂质体。测定其粒径、电位、包封率、体外释药、血浆中稳定性等。并采用四甲基偶氮唑盐〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT〕进行体外抗肿瘤活性研究,以及采用荷肉瘤S180小鼠进行体内抗肿瘤活性研究,考察各组抑瘤率和存活率。结果多西紫杉醇海豹油脂质体的粒径在200 nm左右,Zeta电位为-30~-50 m V,包封率达95%以上。体外释放研究证明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体具有一定的p H敏感性,且推测多西紫杉醇海豹油脂质体具有更强的缓释作用。血浆中稳定性研究证明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体在血浆中较稳定,释放行为缓慢。结论由MTT法结果得多西紫杉醇海豹油脂质体、多西紫杉醇脂肪乳与DTX均表现出较强的细胞毒性作用,且多西紫杉醇海豹油脂质体具有一定的缓释作用。以荷肉瘤S180小鼠为模型的体内抗肿瘤活性研究表明多西紫杉醇脂肪乳与多西紫杉醇海豹油脂质体在血浆中12 h内累积释放量分别为(13.82±0.59)%与(12.91±0.60)%。说明剂型在血浆中较稳定,释放行为缓慢。另外,DTX组小鼠9 d存活率为0,多西紫杉醇脂肪乳组于9 d存活率为93.3%,而多西紫杉醇海豹油脂质体组小鼠9 d存活率为100%,说明多西紫杉醇海豹油脂质体使得耐受剂量提高,降低了药物的不良反应,提高用药安全性与用药的顺应性。
[Abstract]:Objective to investigate the antitumor activity of docetaxella-DTX seal liposome and its comparison with fat emulsion. Methods the prescription was screened by orthogonal design, and the liposome of docetaxelon seal oil was prepared by high pressure emulsion leveling. The particle size of the liposome was determined. Potential, encapsulation efficiency, drug release in vitro, stability in plasma, etc. Antitumor activity in vitro was studied by tetrazolium bromidetran MTTT with tetrazolium bromide MTT, and antitumor activity in vivo in S180 mice was studied by using tetrazolium tetrazolium 5-diphenyltetrazolium tetrazolium (MTTT), a tetrazolium tetrazolium tetrazolium 5-diphenyltetrazolium tetrazolium tetrazolium tetrazolium in vitro. Results the diameter of docetaxel seal liposomes was about 200 nm and the entrapment efficiency was over 95%. The in vitro release studies showed that docetaxel fat emulsion and docetaxel were more than 95%. Seal oil liposomes have a certain pH sensitivity. It is suggested that docetaxel seal oil liposomes have stronger sustained release effect. The stability of docetaxel fat emulsion and docetaxel seal oil liposome is more stable in plasma than that of docetaxel seal oil liposome in plasma. Conclusion docetaxel seal oil liposome, docetaxel fat emulsion and DTX showed strong cytotoxicity by MTT method. The antitumor activity of docetaxel seal liposome in vivo using S180 mice as model showed that docetaxel fat emulsion and docetaxel seal oil liposome were in plasma for 12 h. The cumulative release was 13.82 卤0.59% and 12.91 卤0.60%, respectively. In addition, the survival rate was 0 in DTX group, 93.3 in docetaxel fat emulsion group and 100 in docetaxel seal oil liposome group. Plastids increase the tolerance dose, The safety and compliance of the drug were improved by reducing the adverse drug reactions.
【作者单位】：首都医科大学化学生物学与药学院药剂学系;首都医科大学化学生物学与药学院药药物化学系;
【基金】：“十二五”重大新药创制科技重大专项(2011ZX09302-007-01)~~
【分类号】：R96;TB383.1

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