Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
Nanomedicine. 2011 Dec;7(6):834-40. doi: 10.1016/j.nano.2011.02.001. Epub 2011 Mar 1.
Hormone- and trastuzumab-insensitive breast cancer has limited and ineffective clinical treatment options. This study sought to develop a liposome formulation containing a synergistic combination of vincristine and quercetin, with prolonged drug circulation times and coordinated drug release in vivo, to develop effective treatments against this subtype of breast cancer. The 2:1 molar ratio of vincristine/quercetin showed strong synergism in the hormone- and trastuzumab-insensitive JIMT-1 cells. Liposome co-encapsulation prolonged plasma circulation of the two drugs and maintained the synergistic drug ratio in vivo. Furthermore, the co-encapsulated liposome formulation demonstrated the most effective tumor growth inhibition in the JIMT-1 human breast tumor xenograft in comparison with vehicle control, free quercetin, free vincristine and free vincristine/quercetin combinations. Specifically, only the co-encapsulated liposome formulation exhibited significant antitumor activity at two-thirds of the maximum tolerated dose of vincristine, without significant body weight loss in the animals.
In this study, a novel liposome formulation containing a synergistic combination of vincristine and quercetin was utilized in the treatment of breast cancer. Prolonged drug circulation times and coordinated drug release characterize this effective treatment, which may find its way to clinical applications in the near future.
激素和曲妥珠单抗不敏感的乳腺癌的临床治疗选择有限且效果不佳。本研究旨在开发一种含有长春新碱和槲皮素协同组合的脂质体制剂，该制剂具有延长药物循环时间和体内协调药物释放的特点，从而开发针对这种乳腺癌亚型的有效治疗方法。长春新碱/槲皮素的 2:1 摩尔比在激素和曲妥珠单抗不敏感的 JIMT-1 细胞中表现出强烈的协同作用。脂质体共包封延长了两种药物的血浆循环时间，并维持了体内的协同药物比例。此外，与载体对照、游离槲皮素、游离长春新碱和游离长春新碱/槲皮素组合相比，共包封的脂质体制剂在 JIMT-1 人乳腺癌异种移植模型中显示出最有效的肿瘤生长抑制作用。具体而言，只有共包封的脂质体制剂在长春新碱最大耐受剂量的三分之二时表现出显著的抗肿瘤活性，而动物体重没有明显减轻。
在这项研究中，一种新型的脂质体制剂含有长春新碱和槲皮素的协同组合，用于治疗乳腺癌。这种有效的治疗方法具有延长药物循环时间和协调药物释放的特点，可能在不久的将来会应用于临床。
