Grams Ylva Y, Whitehead Lynne, Cornwell Paul, Bouwstra Joke A
Leiden/Amsterdam Centre for Drug Research, Department of Pharmaceutical Technology, Leiden University, P.O. Box 9502, Einsteinweg 55, 2300 RA Leiden, The Netherlands.
J Control Release. 2004 Aug 27;98(3):367-78. doi: 10.1016/j.jconrel.2004.05.010.
Visualising the penetration pathway of a lipophilic model dye into the hair follicle of fresh unfixed human skin would facilitate optimisation of drug formulations for local delivery to the pilosebaceous unit. A block of fresh human scalp skin was mechanically fixed in a newly designed combination of cutting device/on-line diffusion cell, manual cross-sectioned perpendicular to the skin surface and sealed to create the donor and acceptor compartment. The donor phase consisted of a saturated solution of Bodipy FL C(5) in a citric acid buffer solution. Images were obtained on-line by confocal laser scanning microscopy (CLSM) every 30 min for 16 h. For each time point and each skin region relative intensity values were calculated. The on-line visualisation showed a fast diffusion of the label into the gap of the hair follicle followed by a fluorescent staining in the gap itself. The data strongly indicate that the fluorescence in the cuticle originates mainly from the dye of the gap and not from the surrounding epidermis. The on-line visualisation provides a new and excellent tool to monitor simultaneous changes in distribution profiles in the various skin layers including the hair follicle. This information can be used to determine penetration pathways in the skin.
可视化亲脂性模型染料进入新鲜未固定人体皮肤毛囊的渗透途径，将有助于优化用于局部递送至皮脂腺单位的药物制剂。将一块新鲜的人类头皮皮肤机械固定在新设计的切割装置/在线扩散池组合中，手动垂直于皮肤表面进行横截面切割并密封，以创建供体和受体隔室。供体相由Bodipy FL C(5)在柠檬酸缓冲溶液中的饱和溶液组成。通过共聚焦激光扫描显微镜（CLSM）每30分钟在线获取一次图像，持续16小时。对于每个时间点和每个皮肤区域，计算相对强度值。在线可视化显示标记物快速扩散到毛囊间隙中，随后间隙本身出现荧光染色。数据强烈表明，角质层中的荧光主要源自间隙中的染料，而非周围的表皮。在线可视化提供了一种新的优秀工具，可用于监测包括毛囊在内的各皮肤层中分布情况的同时变化。这些信息可用于确定皮肤中的渗透途径。
