摘要
目的:本研究采用二油基磷脂酰丝氨酸(DOPS)制备包载重组人内皮抑素的胶束,并考察其体内外抑瘤效应。方法:研究DOPS制备胶束的理化性质,考察重组人内皮抑素DOPS胶束对肿瘤细胞生长、鸡胚绒毛尿囊体内血管生长的影响及对H22肝癌荷瘤小鼠的肿瘤抑制效果。结果:制备的重组人内皮抑素DOPS胶束的粒径为(117.7±21.4)nm,Zeta电位为+18.1 mV,包封率为96.54%。该胶束明显抑制MCF-7肿瘤细胞的生长和增殖,抑制率为32.02%;对鸡胚绒毛尿囊血管新生也有明显的抑制作用,剂量越大,抑制作用越强。与单独使用重组人内皮抑素相比,该胶束抑制H22肝癌荷瘤小鼠肿瘤生长,抑制率达到55.42%。结论:以DOPS胶束作为药物载体可有效地增强重组人内皮抑素的抑瘤效应。
Objective： This study is to obtain an effective delivery system for transporting recombinant human endostatin（rhEndostatin） to tumor cell and evaluate its anti-tumor efficiency.Methods： Lipid micelles of dioleoylphosphatidylserine（DOPS） were used to encapsulate rhEndostatin.The corresponding in vitro and in vivo antitumor effects of encapsulated rhEndostatin were observed on MCF-7 cells with 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay.The inhibition of neovascularization was studied on chicken embryo chorioallantoic membrane（CAM）.Results： The mean diameter of the rhEndostatin micelles was（117.7±21.4） nm with narrow size distribution.The entrapment efficiency of the encapsulation was 96.54%.The micellar rhEndostatin significantly inhibited the proliferation of MCF-7 cells in vitro.The antitumor effect of encapsulated rhEndostatin in DOPS micelles was significantly enhanced in the mice bearing H22 tumor and the survival of tumor-bearing mice was prolonged significantly.Neovascularization in CAM was inhibited efficiently compared with the control.Conclusion： It is concluded that rhEndostatin encapsulated in DOPS micelles was more effective in inhibiting tumor growth in vitro and in vivo compared with rhEndostatin.
出处
《药学与临床研究》
2010年第6期516-519,523,共5页
Pharmaceutical and Clinical Research
基金
国家重大新药创制项目(2009ZX09013-635)
江苏省自然科学基金(BK2008150)
