Ganapathi R, Krishan A, Wodinsky I, Zubrod C G, Lesko L J
Cancer Res. 1980 Mar;40(3):630-3.
1-beta-D-Arabinofuranosylcytosine (ara-C) was encapsulated in anionic multilamellar liposomes prepared with different lecithin: cholesterol (L:C) ratios. The chemotherapeutic activity of encapsulated ara-C was compared with comparable doses of ara-C in 0.85% saline solution (single- and multiple-dose schedules) in mice bearing L1210 (i.p.) leukemia. Maximum survival was obtained in animals given injections of ara-C (40 mg/kg) encapsulated in liposomes with a L:C ratio of 1:1. The effect of L:C ratio on survival was not pronounced in multiple-dose schedules. Multiple doses (every 4.5 hr for 3 separate injections) of 40 mg/kg with L:C ratios of 1:1 and 1:0.5 were toxic, resulting in 83 and 50% mortality, respectively, of mice by Day 7. This study shows that drug efflux and in vivo antitumor activity and toxicity of encapsulated ara-C is influenced by the cholesterol content of the liposomal lipid bilayer.
1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷）被包裹于用不同卵磷脂：胆固醇（L:C）比例制备的阴离子多层脂质体中。在携带L1210（腹腔注射）白血病的小鼠中，将包裹的阿糖胞苷的化疗活性与0.85%盐溶液中相当剂量的阿糖胞苷（单剂量和多剂量方案）进行比较。在给予注射L:C比例为1:1的脂质体包裹的阿糖胞苷（40mg/kg）的动物中获得了最大生存期。在多剂量方案中，L:C比例对生存期的影响不明显。L:C比例为1:1和1:0.5的40mg/kg多剂量（每4.5小时进行3次单独注射）具有毒性，到第7天时分别导致83%和50%的小鼠死亡。本研究表明，包裹的阿糖胞苷的药物外排、体内抗肿瘤活性和毒性受脂质体脂质双层胆固醇含量的影响。
