通过脂质体递送9-硝基喜树碱在体内改变内酯/羧酸盐的盐平衡。

Modified lactone/carboxylate salt equilibria in vivo by liposomal delivery of 9-nitro-camptothecin.

作者信息

Chow D S, Gong L, Wolfe M D, Giovanella B C

机构信息

College of Pharmacy, University of Houston, 1441 Moursund St., Texas Medical Center, Houston, TX 77030, USA.

出版信息

Ann N Y Acad Sci. 2000;922:164-74. doi: 10.1111/j.1749-6632.2000.tb07034.x.

DOI:10.1111/j.1749-6632.2000.tb07034.x

PMID:11193891

Abstract

The lactone stability of camptothecins is critical for their anticancer activity. A stable liposomal 9-nitro-camptothecin formulation was developed to circumvent the drawbacks of low aqueous solubility and lactone instability and to provide sustained release of the agent in blood circulation. The potential merits of the formulation were demonstrated by its profoundly improved lactone stability in vivo, favorable pharmacokinetic and biodistribution characteristics in rats, and enhanced preclinical efficacy in tumor-bearing athymic mice.

摘要

喜树碱的内酯稳定性对其抗癌活性至关重要。开发了一种稳定的脂质体9-硝基喜树碱制剂，以克服其水溶性低和内酯不稳定的缺点，并在血液循环中实现该药物的持续释放。该制剂在体内显著提高的内酯稳定性、在大鼠中良好的药代动力学和生物分布特征以及在荷瘤裸鼠中增强的临床前疗效证明了其潜在优点。