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

Study on preparation of cerulenin liposomes and its effects on proliferation of tumor cells in vitro

目的制备浅蓝菌素脂质体并研究其对HER2/neu(erbB-2)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-B r3和SK-Ov3细胞的增殖,IC50分别为9.62和9.32μmol.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-B r3细胞和SK-Ov3细胞有明显的增殖抑制作用,且作用强于游离浅蓝菌素。

Objective To optimize the preparation of cerulenin iposomes and investigate the effect of cerulenin liposomes on proliferation of tumor cells overexpressing HER-2/neu in vitro. Methods Cerulenin embedded in liposomes was assayed by HPLC and the embedding rate of cerulenin was calculated. Particle size and distribution 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 ICso 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.