Rubbing actions are often conducted to apply topical formulations onto the skin. Although rubbing was found to increase the skin permeation of drugs, few reports have revealed whether rubbing enhanced either drug permeation through the stratum corneum (SC) or hair follicles (HFs) pathways, or through both. In the present study, we investigated the effects of rubbing on caffeine (CAF) distribution in the SC and HFs. The effect of rubbing direction on the skin penetration of CAF was also investigated. The skin concentration of CAF and its cumulative permeation amount were increased clearly by rubbing. More than six times higher CAF concentrations in the viable epidermis and dermis were observed 5 min after rubbing application compared with no rubbing. On the other hand, slightly increased CAF concentrations were observed in the SC, suggesting that CAF was delivered through the HF pathway by rubbing. Rubbing against the natural hair direction provided the highest skin permeation as well as skin concentrations. Changes in the morphology of the HF opening area might be related to the enhancement effect. These results may provide useful information to understand the effect of rubbing on the skin permeation of applied drugs.

通常进行摩擦动作以将局部制剂施加到皮肤上。尽管发现摩擦会增加药物的皮肤渗透性，但很少有报道揭示摩擦是通过角质层（SC）还是毛囊（HFs）途径，或同时通过这两种途径来增强药物渗透性。在本研究中，我们调查了摩擦对SC和HF中咖啡因（CAF）分布的影响。还研究了摩擦方向对CAF皮肤渗透的影响。通过摩擦，CAF的皮肤浓度及其累积渗透量明显增加。与不揉搓相比，揉搓后5分钟观察到活的表皮和真皮中CAF浓度高出六倍以上。另一方面，在SC中观察到CAF浓度略有增加，提示CAF是通过摩擦通过HF途径传递的。顺着自然的头发方向揉搓可提供最高的皮肤渗透性和皮肤浓度。HF开口区域的形态变化可能与增强效果有关。这些结果可能提供有用的信息，以了解摩擦对所用药物皮肤渗透的影响。