固醇修饰的脂:胆固醇和脂仿真体,具有改善的生物膜特性
Zhaohua Huang1, Francis C Szoka
1Department of Pharmaceutical Chemistry, School of Pharmacy, University of California at San Francisco, San Francisco, California 94143-0912, USA.
Journal of the American Chemical Society
|October 28, 2008
概括
固醇修饰脂 (SML) 在双层内固胆固醇,保持膜性质. 这些SML脂质体表现出增强的稳定性和药物传递潜力,抵抗血清效应,并为膜研究提供了一种新工具.
科学领域:
- 生物化学 生物化学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 胆固醇对膜结构和功能至关重要.
- 自由胆固醇可以从脂质体中提取出来,影响药物输送.
- 了解胆固醇在脂质二层中的作用是开发稳定的脂质体配方的关键.
研究的目的:
- 为了合成和表征固醇修饰的甘油脂 (SML).
- 为了研究如何对胆固醇与脂的合性定会影响其在脂质双层中的行为.
- 评估SML脂质体在药物输送应用中的潜力.
主要方法:
- 用胆固醇在sn-1或sn-2位置合成固醇修饰的甘油脂 (SML).
- 使用单独使用SML或与二甲基甘油脂混合物形成脂质体.
- 对膜凝结特性,热热变相转换和透诱导的内容泄漏的分析.
- 在血清中评估脂质体稳定性和体内测试用多克索鲁比辛载入的SML脂质体的疗效.
主要成果:
- 无论附着位置如何,SML保留了胆固醇的膜凝结特性.
- 在大约30mol%的SML中,SML脂质体消除了温度转变相位.
- 脂质体含量泄漏取决于胆固醇链接,但一般类似于传统的脂质体.
- SML脂质体对血清诱导的内容释放表现出异常的耐药性.
- 载有多克索鲁比的SML脂质体在治疗小鼠结肠癌方面表现出与多克西尔相当的疗效.
结论:
- 胆固醇与脂 (SML) 的合性定稳定双层,而不会影响胆固醇的基本膜性质.
- SML脂质体对血清和减少的交换提供了增强的稳定性,这表明药物输送概况得到了改进.
- SMLs代表了生物物理膜研究的新工具,并为先进的脂质体药物递送系统提供了希望.
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