Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals
Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals
复制标题
毛囊通路对局部应用和暴露的化学品的皮肤总渗透的贡献
作者：
Fadli Mohd;H. Todo;M. Yoshimoto;Eddy Yusuf;K. Sugibayashi
一般来说，局部施用或暴露的化学物质的血液和皮肤浓度曲线以及稳态皮肤浓度可以从体外皮肤渗透曲线计算出来。然而，这些计算方法特别适用于主要途径是通过角质层的化学品。如果可以详细地获得毛囊对化学物质在皮肤中渗透的贡献，就可以更精确地预测它们在血液和皮肤中的浓度。在本研究中，通过体外皮肤渗透实验，通过毛囊堵塞和未堵塞的皮肤渗透系数之间的差异，计算了毛囊途径对局部应用或暴露的化学物质皮肤渗透的贡献。所得结果表明，利用化学物质的亲脂性可以预测毛囊通路的贡献。对于亲水化学物质（正辛醇/水分配系数的对数(log Ko/w) < 0），由于毛囊堵塞导致的渗透减少比亲脂化学物质（log Ko/w≥0）更大。此外，随着log Ko/w的增加，这种降低的比例也随之降低。考虑毛囊通路将有助于研究局部应用或暴露于化学品后的有效性和安全性，因为由于毛囊密度的差异，皮肤的渗透和处置应在不同身体部位的皮肤中有所不同。
Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals’ lipophilicity. For hydrophilic chemicals (logarithm of n-octanol/water partition coefficient (log Ko/w) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log Ko/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log Ko/w. This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles.