van Kuijk-Meuwissen M E, Junginger H E, Bouwstra J A
Division of Pharmaceutical Technology, Leiden/Amsterdam Center of Drug Research, Leiden University, P.O. Box 9502, Leiden 2300RA,The Netherlands.
Biochim Biophys Acta. 1998 Apr 22;1371(1):31-9. doi: 10.1016/s0005-2736(97)00273-3.
One major problem in (trans)dermal drug delivery is the low penetration rate of drugs through the barrier of the skin. Encapsulation of a drug in lipid vesicles is one strategy to increase the penetration rate of a drug across the skin. In this study, the interactions between fluorescent-labelled liposomes and skin are visualized by confocal laser scanning microscopy (CLSM). Bilayer labelled gel-state and liquid-state liposomes (conventional or with flexible bilayers) were non-occlusively applied on human skin in vitro. The penetration pathway and penetration depth of the lipophilic fluorescent label into the skin were visualized. From the CLSM images, it was clear that the label applied in micelles and gel-state liposomes did not penetrate as deep into the skin as the label applied in liquid-state vesicles. Among the liquid-state vesicles, the suspensions with the flexible bilayers showed the highest fluorescence intensity in the dermis. Thus, the thermodynamic state of the bilayer and, to a smaller extent, the flexibility of the bilayer influence, strongly the penetration depth of the label into the skin. The label applied non-occlusively in flexible liposomes penetrated deeper into the skin than after occlusive application.
（经）皮给药的一个主要问题是药物透过皮肤屏障的渗透率较低。将药物包裹在脂质囊泡中是提高药物经皮渗透率的一种策略。在本研究中，通过共聚焦激光扫描显微镜（CLSM）观察了荧光标记脂质体与皮肤之间的相互作用。将双层标记的凝胶态和液态脂质体（传统的或具有柔性双层的）非封闭地应用于体外人体皮肤。观察到亲脂性荧光标记物进入皮肤的渗透途径和渗透深度。从CLSM图像可以清楚地看出，应用于胶束和凝胶态脂质体中的标记物没有像应用于液态囊泡中的标记物那样深入皮肤。在液态囊泡中，具有柔性双层的悬浮液在真皮中显示出最高的荧光强度。因此，双层的热力学状态以及在较小程度上双层的柔性强烈影响标记物进入皮肤的渗透深度。非封闭地应用于柔性脂质体中的标记物比封闭应用后更深入皮肤。
