OBJECTIVE: Skin appendages including hair follicles (hfs) and the stratum corneum (sc) are beginning to be recognized as important permeation pathways for the skin permeation of drugs, but their detailed role is not yet clear. To investigate the contribution of hfs to drug permeation, we conducted skin permeation tests by controlling the hf contribution with a hf-plugging method. METHOD: Lidocaine (LC) and fluorescein isothiocyanate-dextran 4 kDa (FD-4) were selected as model drugs and pig ear skin was used as model skin. RESULTS: Skin permeabilities of ionized LC and FD-4 decreased with hf-plugging, whereas no change was observed for the skin permeation of unionized LC. A fairly good correlation was found for ionized LC and FD-4 between skin permeability and the number of hfs plugged. Permeation parameters of model drugs for both skin pathways were calculated utilizing Fick's second law of diffusion. Consequently, the sc pathway could highly contribute to the permeation of unionized LC, since unionized LC shows markedly high partition to the sc. In contrast, the hf pathway could contribute to the permeation of ionized LC and FD-4, since these had high distributions to the hf pathway in spite of its very small surface area relative to whole skin surface area. CONCLUSION: The hf pathway must be important for the skin permeation of ionized compounds and hydrophilic high molecular compounds. hf-plugging is also a useful method for assessing the skin permeability of compounds through the hf pathway.
OBJECTIVE: Skin appendages including hair follicles (hfs) and the stratum corneum (sc) are beginning to be recognized as important permeation pathways for the skin permeation of drugs, but their detailed role is not yet clear. To investigate the contribution of hfs to drug permeation, we conducted skin permeation tests by controlling the hf contribution with a hf-plugging method. METHOD:Lidocaine (LC) and fluorescein isothiocyanate-dextran 4 kDa (FD-4) were selected as model drugs and pig ear skin was used as model skin. RESULTS: Skin permeabilities of ionizedLC and FD-4 decreased with hf-plugging, whereas no change was observed for the skin permeation of unionized LC. A fairly good correlation was found for ionizedLC and FD-4 between skin permeability and the number of hfs plugged. Permeation parameters of model drugs for both skin pathways were calculated utilizing Fick's second law of diffusion. Consequently, the sc pathway could highly contribute to the permeation of unionized LC, since unionized LC shows markedly high partition to the sc. In contrast, the hf pathway could contribute to the permeation of ionizedLC and FD-4, since these had high distributions to the hf pathway in spite of its very small surface area relative to whole skin surface area. CONCLUSION: The hf pathway must be important for the skin permeation of ionized compounds and hydrophilic high molecular compounds. hf-plugging is also a useful method for assessing the skin permeability of compounds through the hf pathway.