浅蓝菌素脂质体的制备及其对肿瘤细胞体外增殖影响的研究_药学论文.docVIP

浅蓝菌素脂质体的制备及其对肿瘤细胞体外增殖影响的研究_药学论文 浅蓝菌素脂质体的制备及其对肿瘤细胞体外增殖影响的研究_药学论文 【摘要】 　　目的 制备浅蓝菌素脂质体并研究其对HER2/neu(erbB原癌基因过表达肿瘤细胞株体外增殖的影响。方法 采用超声薄膜分散法制备浅蓝菌素脂质体；正交设计优化处方；HPLC法测定药物包封率及脂质体中药物浓度；离心加速实验及冷藏实验考察脂质体稳定性；活细胞计数法测定细胞生长曲线；MTT法测定游离浅蓝菌素及浅蓝菌素脂质体对细胞的增殖抑制作用。结果 浅蓝菌素脂质体的平均粒径为134.3 nm，稳定性良好，最佳处方条件下药物包封率为(53.45±3.67)%，脂质体中药物质量浓度为(1.126±0.065) mg/mL，剂量依赖性抑制SK和SK细胞的增殖，IC50分别为9.62和9.32 μmol·L-1。结论 该制备工艺和处方可行，所制备的浅蓝菌素脂质体对SK细胞和SK细胞有明显的增殖抑制作用，且作用强于游离浅蓝菌素。 【关键词】 浅蓝菌素 脂质体 包封率 肿瘤细胞 IC50 　　Abstract:Objective To optimize the preparation of cerulenin iposomes and investigate the effect of cerulenin liposomes on proliferation of tumor cells overexpressing HERistribution of cerulenin liposomes were investigated by laser scatter and stability of liposomes was investigated by centrifugal acceleration experiment and deep freezing. The growth curves of cells treated with cerulenin liposomes at different concentrations were determined by counting the cell number and IC50 of cerulenin liposomes was determined by MTT method. Results The average diameter of cerulenin liposomes was 134.3 nm with good stability. The embedding rate of cerulenin into liposomes was 53.45%, and the concentration of cerulenin in liposomes was 1.126 mg/mL. The liposomes inhibited the growth of SKBr3 and SKOv3 cells in vitro in a dosedependent manner and the IC50 of cerulenin liposomes on SKBr3 and SKOv3 cells was 9.62×10-6 and 9.32×10-6 mol/L respectively. Conclusion The cerulenin liposomes that were prepared with the modified formulation inhibited the proliferation of SKBr3 and SKOv3 cells in vitro with IC50 less than those of free cerulenin. 　　Key words:Cerulenin; liposomes; embedding rate; tumor cells; IC50 　　近年来研究发现脂肪酸合成酶(FAS)在多种恶性肿瘤如乳腺癌、卵巢癌中呈高表达，并且与肿瘤的恶性程度及预后相关［1，2］。FAS的抑制剂浅蓝菌素通过与脂肪酸合成酶复合体系的β酮脂酰合酶末端丝氨酸的结合，形成内酰胺从而使FAS失活，但只有HER2/neu(erbB原癌基因过表达的肿瘤细胞株才对浅蓝菌素敏感［1］。 　　 　　浅蓝菌素(cerulenin, CE)为浅蓝头孢霉菌的次级代谢产物，研究发现其也可从多种微生物及动物组织中分离提取［3］。除了用于治疗肥胖症外，近几年还发现浅蓝菌素具有抗真菌［4］、抗病毒［5］、抗癌［6］等药理作用，引起了研究者的极大兴趣。但该化合物水溶性差（溶解度约为0.3 mg/mL）、毒副作用较强，且化学