Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Dermatology, Venereology, and Allergology, Center of Experimental and Applied Cutaneous Physiology, Berlin, Germany,
Merck KGaA, Darmstadt, Germany.
Skin Pharmacol Physiol. 2020;33(2):117-126. doi: 10.1159/000505839. Epub 2020 Feb 11.
The skin represents a drug delivery portal. The establishment of a skin model capable of distinguishing between the follicular and intercellular penetration pathways remains a challenge. The study described herein was aimed at showing the influence of two nail varnishes as closure material and four application techniques to spread the active pharmaceutical ingredient (API) on a successful follicular closure without inducing penetration-enhancing effects.
For all experiments, ex vivo porcine ear skin was used. In study design A, a standard and a solvent-free nail varnish were compared. It was tested whether the different application techniques (spreading with pipette, careful finger massage, 5-Hz finger massage, 5-Hz automatic massage) potentially destroy an intact follicular closure. Laser scanning microscopy imaging was used to measure if the model drug (fluorescein sodium salt) penetrated into the hair follicles. Study design B investigated how the penetration is affected when applying standard nail varnish containing solvents to skin. It was tested if the varnish blocks the API (caffeine) on completely covered areas and if adjacent areas show increased penetration. Furthermore, lateral diffusion of the API was investigated. After 20 h, the skin layers were separated by tape stripping and heat separation. The tissue samples were homogenized. Caffeine was quantified by chromatography.
In study design A, the standard nail varnish showed a secure follicular closure, while the solvent-free nail varnish was not able to prevent follicular penetration. Moreover, rapid application techniques were found to destroy an intact follicular closure. Only the two most gentle application techniques kept the follicular closing intact. In study design B, no caffeine was detected in both skin areas that were completely covered. Since no significant difference in caffeine penetration between the two uncovered groups was found, any influence of the applied closure material on adjacent areas was excluded.
This study clearly demonstrates that a standard nail varnish in combination with a gentle application technique of the API provides a secure follicular closure. The presented study only investigated the closure for the substances caffeine and fluorescein sodium salt. The results might not be transferable to all kinds of APIs.
皮肤是药物传递的门户。建立一种能够区分毛囊和细胞间渗透途径的皮肤模型仍然是一个挑战。本研究旨在展示两种指甲油作为封闭材料的影响，以及四种涂抹技术将活性药物成分（API）扩散到成功的毛囊封闭而不诱导渗透增强作用。
所有实验均使用离体猪耳皮肤。在研究设计 A 中，比较了一种标准指甲油和一种无溶剂指甲油。测试了不同的涂抹技术（用移液器涂抹、小心手指按摩、5-Hz 手指按摩、5-Hz 自动按摩）是否会破坏完整的毛囊封闭。激光扫描显微镜成像用于测量模型药物（荧光素钠盐）是否渗透到毛囊中。研究设计 B 研究了在皮肤涂抹含溶剂的标准指甲油时如何影响渗透。测试了指甲油是否能阻止 API（咖啡因）在完全覆盖的区域，以及相邻区域是否显示出增加的渗透。此外，还研究了 API 的侧向扩散。20 小时后，用胶带剥离和热分离将皮肤层分离。将组织样本匀浆。通过色谱法定量咖啡因。
在研究设计 A 中，标准指甲油显示出安全的毛囊封闭，而无溶剂指甲油则不能防止毛囊渗透。此外，快速涂抹技术被发现会破坏完整的毛囊封闭。只有两种最温和的涂抹技术能保持毛囊关闭完整。在研究设计 B 中，完全覆盖的两个皮肤区域均未检测到咖啡因。由于未发现两个未覆盖组之间咖啡因渗透的显著差异，因此排除了应用封闭材料对相邻区域的任何影响。
本研究清楚地表明，标准指甲油与 API 的温和涂抹技术相结合，可提供安全的毛囊封闭。本研究仅研究了咖啡因和荧光素钠盐这两种物质的封闭作用。结果可能不适用于所有类型的 API。
