【摘要】 目的建立半乳糖化氟尿嘧啶前体脂质体的制备方法,并对该制剂体外细胞毒性进行初步研究。方法采用逆向蒸发-冷冻干燥法制备前体脂质体,CCK-8法分别考察半乳糖化氟尿嘧啶脂质体对SMMC-7721和MCF7的细胞毒性,Annexin V-FITC/PI流式细胞分析法分别检测原药和半乳糖化氟尿嘧啶前体脂质体对SMMC-7721细胞株和MCF7细胞株的细胞凋亡率。结果该方法制得的前体脂质体呈球形或近球形,粒径为(188. 2±2. 4) nm,包封率为(71. 2±1. 0)%,在4℃贮120 d渗漏率(4. 1±0. 9)%,对于SMMC-7721细胞,半乳糖化氟尿嘧啶前体脂质体的抑制率最高,对于MCF7细胞,半乳糖化氟尿嘧啶前体脂质体和氟尿嘧啶前体脂质体的抑制率无明显差别,但均高于原药。原药对MCF7细胞有较强的诱导细胞凋亡能力,半乳糖化氟尿嘧啶前体脂质体对SMMC-7721细胞有较强的诱导细胞凋亡能力。结论该方法制得的前体脂质体包封率高,稳定性好,初步判定半乳糖化氟尿嘧啶前体脂质体有一定的主动肝靶向性。更多还原

【Abstract】 Objective To establish a preparation method of galactosylated fluorouracil precursor liposome and to study the cytotoxicity of the preparation in vitro. Methods Precursor liposomes were prepared by reverse evaporating-freezing-drying method. The cytotoxicity of lactosylated fluorouracil liposomes against SMMC-7721 and MCF7 was investigated by CCK-8 method. The apoptosis rate of the prodrug and galactosylated fluorouracil precursor liposome on SMMC-7721 cell line and MCF7 cell line was detected by Annexin V-FITC/PI flow cytometry analysis. Results The precursor liposome prepared by the method was spherical or nearly spherical,and the particle size was( 188. 2 ± 2. 4) nm,the encapsulation efficiency was( 71. 2 ± 1. 0) %,and the leakage rate was( 4. 1 ±0. 9) % stored at 4 ℃ for 120 days. The inhibition rate of galactosylated fluorouracil precursor liposome was the highest for SMMC-7721 cells,and there was no significant difference in the inhibition rate of galactosylated fluorouracil precursor liposome and fluorouracil precursor liposome for MCF7 cells,but all of them were higher than the original drug. The original drug had strong ability to induce apoptosis of MCF7 cells,and galactosylated fluorouracil precursor liposome had strong ability to induce apoptosis of SMMC-7721 cells. Conclusion The precursor liposomes prepared by this method have high encapsulation efficiency and good stability. It is preliminarily determined that galactosylated fluorouracil precursor liposomes have certain active liver-targeting properties.更多还原