WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1-3]. * In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems. * Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5]. * Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1]. WHAT THIS STUDY ADDS * The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances. * We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo. * These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures. AIMS The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. METHODS Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. RESULTS Caffeine (3.75 ng ml(-1)) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml(-1)). Highest values (11.75 ng caffeine ml(-1)) were found 1 h after application when the follicles were open. CONCLUSIONS Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

中文翻译：

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毛囊在经皮吸收咖啡因中的作用。

关于该主题的已知信息 * 近年来，有人提出毛囊是药物和化学品进入皮肤的重要分流途径 [1-3]。* 体外研究表明皮肤附属物对亲水性化合物渗透皮肤的重要性 [4]。由于缺乏合适的分析方法或合适的动物模型系统，体内滤泡渗透的研究一直很困难。* 最近，描述了一种通过选择性闭合毛囊来量化体内毛囊渗透的新方法 [5]。* 咖啡因经常用于皮肤渗透实验，作为高水溶性化合物的模型。闭塞 [6] 和皮肤厚度 [7] 似乎对咖啡因的渗透影响不大。然而，咖啡因的经皮吸收率在人体体内表现出区域皮肤差异[1]。本研究的新增内容 * 本研究的结果表明，咖啡因的快速药物传递是通过分流途径发生的。因此，毛囊是我们保护鞘中的相当薄弱点，可以防止亲水性物质渗透到身体中。* 我们表明，体内咖啡因的毛囊渗透和毛囊间扩散之间存在定量差异。* 这些发现对于局部应用药物和化妆品的开发和优化具有重要意义。此外，在制定皮肤保护措施时必须考虑这些特性。目的 皮肤及其附属物是我们抵御环境的保护屏障，是维持体内平衡所必需的。关于物质渗透到皮肤中的假设假设通过角质层的脂质域扩散。据信，虽然毛囊代表了屏障的弱点，但它们在经皮穿透过程中起着次要作用。以前对毛囊渗透的研究主要解决了系统和技术问题。我们的研究利用了体内毛囊孔的选择性闭合技术，用于比较人体对咖啡因的毛囊间和毛囊吸收率。方法 用微滴的特殊清漆蜡混合物在体内封闭皮肤划定区域内的每个毛囊。溶液中的咖啡因被局部应用，并通过新的表面电离质谱 (SI/MS) 技术测量经皮吸收到血液中，这使得可以明确区分局部应用物质的毛囊间和毛囊渗透。结果 当毛囊保持开放时，局部应用 5 分钟后，在血液样本中检测到咖啡因 (3.75 ng ml(-1))。当卵泡被阻塞时，20 分钟后可检测到咖啡因 (2.45 ng ml(-1))。当卵泡打开时，在应用 1 小时后发现最高值（11.75 ng 咖啡因 ml(-1)）。结论 我们的研究结果表明，毛囊是我们保护鞘中针对某些亲水性药物的相当弱点，并且可能允许快速递送局部应用的物质。这使得可以明确区分局部应用物质的毛囊间和毛囊渗透。结果 当毛囊保持开放时，局部应用 5 分钟后，在血液样本中检测到咖啡因 (3.75 ng ml(-1))。当卵泡被阻塞时，20 分钟后可检测到咖啡因 (2.45 ng ml(-1))。当卵泡打开时，在应用 1 小时后发现最高值（11.75 ng 咖啡因 ml(-1)）。结论 我们的研究结果表明，毛囊是我们保护鞘中针对某些亲水性药物的相当弱点，并且可能允许快速递送局部应用的物质。这使得可以明确区分局部应用物质的毛囊间和毛囊渗透。结果 当毛囊保持开放时，局部应用 5 分钟后，在血液样本中检测到咖啡因 (3.75 ng ml(-1))。当卵泡被阻塞时，20 分钟后可检测到咖啡因 (2.45 ng ml(-1))。当卵泡打开时，在应用 1 小时后发现最高值（11.75 ng 咖啡因 ml(-1)）。结论 我们的研究结果表明，毛囊是我们针对某些亲水性药物的保护鞘中相当大的弱点，并且可能允许快速递送局部应用的物质。局部应用后 5 分钟，此时毛囊保持开放。当毛囊被阻塞时，20 分钟后可检测到咖啡因 (2.45 ng ml(-1))。当卵泡打开时，在应用 1 小时后发现最高值（11.75 ng 咖啡因 ml(-1)）。结论 我们的研究结果表明，毛囊是我们保护鞘中针对某些亲水性药物的相当弱点，并且可能允许快速递送局部应用的物质。局部应用后 5 分钟，此时毛囊保持开放。当卵泡被阻塞时，20 分钟后可检测到咖啡因 (2.45 ng ml(-1))。当卵泡打开时，在应用 1 小时后发现最高值（11.75 ng 咖啡因 ml(-1)）。结论 我们的研究结果表明，毛囊是我们保护鞘中针对某些亲水性药物的相当弱点，并且可能允许快速递送局部应用的物质。