一种多功能前药物方法,用于脂质体内核载荷水不溶性坎普托西因抗癌药物
Xinli Liu1, Bert C Lynn, Junhong Zhang
1Department of Chemistry and Pharmaceutical Sciences, Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
Journal of the American Chemical Society
|June 27, 2002
概括
一种新的前药物策略使得水不可溶的坎普托塞辛能够通过脂质体加载. 这种方法有助于瘤向和在瘤部位控制活性坎普托西的释放.
科学领域:
- 制药化学 制药化学 制药化学
- 药物输送系统 药物输送系统
- 纳米技术纳米技术
背景情况:
- 坎普托素是强大的抗癌剂,水溶性差,限制了它们的临床应用.
- 脂质体配方提供了一种改善药物溶解性和药物输送的策略.
- 有效地将不溶于水的药物装入脂质体仍然是一个挑战.
研究的目的:
- 开发一种多功能前药物策略,有效地将不溶于水的坎普托塞辛装入脂质体.
- 创建一个前药物系统,以促进在瘤部位释放活性药物.
- 为了使瘤向输送脂友性坎普托塞辛类似物.
主要方法:
- 活跃的坎普托塞辛类型的转化为omega-aminoalkanoanic 前药.
- 利用前药物的氨基组来增强水溶性和对硫酸盐梯度的响应性,用于脂质体负载.
- 在生理pH下设计前药物进行非酶分解和活性药物释放.
主要成果:
- 前药物策略成功地促进了坎普托塞辛在脂质体水核中的活跃加载.
- 前药在生理pH (≥7) 时经历循环和快速非酶分解,释放出活性坎普托西因.
- 活性剂形成的速度可以通过改变基间距长度 (n) 来调节.
结论:
- 这种新的脂质体前药物策略提供了一种多功能系统,用于输送不溶于水的坎普托素,包括SN-38,9-尼托坎普托素和DB-67.
- 这种方法为向瘤治疗提供了潜在的潜力,具有可控制的药物释放动力学.
- 这种方法克服了与坎普托塞辛类型的可溶性差相关的局限性.
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