摘要
为提高长春新碱(VCR)的抗肿瘤活性并降低其毒副作用,利用聚乙二醇衍生化磷脂酰乙醇胺(PEG-PE)聚合物胶束作为载体制备了包载VCR的PEG-PE胶束(VCR胶束),对其理化性质和体外抗肿瘤活性进行研究.采用透射电镜观察胶束的外观形态,动态光散射法测定粒径和粒度分布,HPLC法测定包封率和体外释放度,MTT法测定VCR胶束及游离VCR对MCF-7细胞的毒性.透射电镜负染照片显示,VCR胶束呈不规则的球状结构,粒度分布窄而均一,平均粒径在(11.1±0.1)nm;VCR能有效被PEG-PE胶束包载,VCR与PEG-PE的摩尔比在1∶2～1∶10的范围内包载量均大于95%;体外释放度和耐稀释试验结果表明,VCR胶束在HBS和血清(pH7.0)两种释放介质中稳定,释放符合一级动力学释药模型;体外细胞毒试验表明,VCR胶束能显著提高VCR对MCF-7细胞生长的抑制作用.制得的VCR纳米胶束具有良好的稳定性、较高包封率和显著提高VCR的抗肿瘤活性,表明PEG-PE胶束将是VCR的一个高效输送载体.
Vincristine （VCR） encapsulated in phospholipid micelles （micellar VCR） were made of polyethylene glycol phosphatidyl ethanolamine （PEG-PE） to improve its effect of growth inhibition on breast tumor cells and to decrease its drug toxicity. The morphological examination of micellar VCR was performed by transmission electron microscope （TEM）. The mean particle size and size distribution were determined by dynamic light scattering （DLS）. The entrapment efficiency and release behavior of VCR in micelles were investigated by reversed-phase high-performance liquid chromatography （HPLC）. The MTT method was employed to test the cytotoxicity of VCR-encapsulated micelles and free VCR in the MCF-7 cells. The micellar VCR exhibited an irregular spherical shape from TEM photographs. VCR can be efficiently encapsulated in PEG-PE micelles that having high entrapment efficiency （95%） when using the molar ratios of VCR/PEG-PE from 1 ： 2 to 1 ： 10. The mean diameter of the micellar VCR was （11.1 ± 0.1） nm with narrow size distribution. The results of release and dilution experiments indicated that the micellar VCR was stable in both HBS and serum （pH 7.0）, and the release profile of VCR from micelles can be well described by one-order kinetic equation （r = 0.9997）. The cytotoxic activity of VCR encapsulated PEG-PE micelles demonstrated high inhibitory effect on MCF-7 cell growth compared to the free VCR. It is concluded that VCR encapsulated in PEG-PE micelles were stable and have high drug entrapment efficiency and high effect of growth inhibition in vitro. PEG-PE micelles may be promising vectors for delivery of VCR into tumor in vivo.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2006年第8期769-774,共6页
Progress In Biochemistry and Biophysics
基金
中国科学院知识创新工程重要方向项目(kjcx2-sw-h12-01).~~
关键词
长春新碱(VCR)
胶束
生长抑制
vincristine, PEG-PE micelles, growth inhibition of tumor cells
