Vaage J, Donovan D, Mayhew E, Uster P, Woodle M
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Int J Cancer. 1993 Jul 30;54(6):959-64. doi: 10.1002/ijc.2910540616.
This study tested the therapeutic effects of vincristine sulfate and doxorubicin hydrochloride, each drug in 2 different formulations: (i) as a solution in saline, and (ii) encapsulated in sterically stabilized, long-circulating liposomes composed of hydrogenated soy-phosphatidylcholine/cholesterol/polyethylene-glycerol-disteroyl++ +- phosphatidylethanolamine. The 4 drug preparations were used to treat s.c. implants of the mouse mammary carcinoma MC2. The drugs were given by i.v. injection over 15 to 18 days, starting 3 days after tumor implantation. The single-drug therapeutic effects of vincristine (S-VCR) and doxorubicin (Doxil) in liposomes were compared, and the 2 preparations were also tested in alternate and in simultaneous combinations. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mice. Alternate, semi-weekly injection of both drugs gave the best therapeutic effect. Prolonged circulation time with increased accumulation in tumors are considered likely reasons for the improved therapeutic efficacy of both drugs when encapsulated in these liposomes.
本研究测试了硫酸长春新碱和盐酸多柔比星的治疗效果，每种药物有2种不同剂型：（i）盐溶液剂型，（ii）包封于由氢化大豆磷脂酰胆碱/胆固醇/聚乙二醇 - 二硬脂酰磷脂酰乙醇胺组成的空间稳定、长循环脂质体中。这4种药物制剂用于治疗小鼠乳腺癌MC2的皮下植入瘤。在肿瘤植入3天后开始，通过静脉注射给药，持续15至18天。比较了长春新碱（S - VCR）和多柔比星（Doxil）脂质体剂型的单药治疗效果，并且这2种制剂还进行了交替和联合给药测试。这些长春新碱和多柔比星的新型脂质体制剂在治愈小鼠方面比游离药物显著更有效。两种药物每周交替注射一次产生了最佳治疗效果。当包封于这些脂质体中时，循环时间延长且在肿瘤中的蓄积增加被认为是这两种药物治疗效果改善的可能原因。
