开发一种方法来研究局部产品药理动力学中的 perfusion 效应
Saara K Luna1, M Alice Maciel Tabosa2, Ting Chean Khoo2
1Wellman Center for Photomedicine, Massachusetts General Hospital, 149 13th St, Charlestown, 02129, MA, USA; Department of Molecular and Cellular Biology, Harvard University, 52 Oxford St, Cambridge, 02138, MA, USA.
这项研究引入了一种使用刺激拉曼散射 (SRS) 显微镜测量皮肤 perfusion 如何影响局部药物吸收 in vivo 的新方法. 结果显示, perfusion 显著影响药物吸收和在皮肤中的分布.
科学领域:
- 药理学 药理学是指药理学的学科.
- 皮肤病学 皮肤病学
- 生物物理学的生物物理.
背景情况:
- 局部药物输送由于皮肤复杂的屏障而面临挑战.
- 现有的药理动力学评估方法通常仅限于体外分析.
- 在体内输液显著影响局部药物吸收和处置.
研究的目的:
- 开发和验证一种新的体内方法,用于评估 perfusion 对局部药物吸收的影响.
- 量化皮肤输液对小鼠皮肤中tazarotene药理学的影响.
- 在 perfused 和 non-perfused 条件下,比较脂质丰富皮肤区域与脂质贫乏皮肤区域的药物透率.
主要方法:
- 利用刺激拉曼散射 (SRS) 显微镜进行局部药物透的化学特异性,时间分辨率成像.
- 采用一对鼠标耳皮肤模型,比较体内 (透) 和体外 (非透) 条件.
- 在角层和脂质腺体中量化的tazarotene度和药理学参数 (Tmax,Cmax,AUC).
主要成果:
- 在体内和体外条件之间观察到tazarotene度-时间概况和药理动力学参数的显著差异.
- 与非 perfused (ex vivo) 皮肤相比, perfusion (体内) 导致tazarotene的透和消除增加.
- 在脂质丰富和脂质贫乏区域之间注意到吸收的变化,受 perfusion 状态的影响.
结论:
- 开发的SRS显微镜方法有效地评估了in vivo perfusion对局部药物吸收的影响.
- 皮肤输液是影响局部药物处置和疗效的关键因素.
- 了解 perfusion 的作用有助于开发有效的局部药物输送系统.
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