Evaluation of percutaneous absorption promoters by means of solid fractal analysis of skin stratum corneum

为评价d-柠檬烯和氮酮等促吸收剂对无毛大鼠皮肤角质层的病理损伤，测定了皮肤角质层的固体分形维数。作为一种皮肤系统模型，我们将含有这些促进剂的酒精水凝胶应用于无毛大鼠腹部皮肤。切除敷处皮肤，用戊二醛和锇酸固定，然后冻干。用激光共聚焦显微镜扫描皮肤表面，并将皮肤表面图像数据输入计算机。在显示器上重建皮肤表面结构为等高线映射图像。然后基于扩展盒计数算法估计固体分形维数。未经处理的皮肤表面固体分形维数为2.17。用含有d-柠檬烯的水凝胶处理皮肤后，分形维数明显降低。另一方面，氮酮对皮肤分形维数的降低程度较差。分形维数的下降可能是由于皮肤结构的平滑，这将是由于皮肤浅部的水化和/或水肿形成造成的。促进剂引起的皮肤表面结构变化可以量化为非积分的固体分形维数和皮肤截面的表面分形维数。这表明分形分析作为一种评估皮肤损伤的新方法是有用和可靠的。

Solid fractal dimension of skin stratum corneum was determined in order to evaluate the pathological damages evoked by percutaneous absorption promoters such as d-limonene and Azone in the hairless rat. As a model dermatological system, alcoholic hydrogels containing each of these promoters were applied to the hairless rat abdominal skin. The application site of the skin was excised, fixed with glutaraldehyde and osmic acid, and then lyophilized. The skin surface was scanned with a confocal laser microscope and the image data of skin surface were fed into a computer. The skin surface structure was reconstructed as a contour mapping image on the display. The solid fractal dimension was then estimated based on the extended box-counting algorithm.The solid fractal dimension of untreated skin surface was estimated to be 2.17. The fractal dimension markedly decreased when the skin was treated with hydrogels containing d-limonene. On the other hand, the degree of decrease in fractal dimension was poor when Azone was applied to the skin. The decrease of fractal dimension may be attributed to the smoothing of the skin structure, which will be caused by the hydration and/or edema formation in the shallow part of the skin.The structure change of skin surface evoked by the promoters can be quantified as a nonintegral solid fractal dimension as well as the surface fractal dimension of skin cross section. This suggests the usefulness and reliability of the fractal analysis as a novel method for evaluating the skin damage.