Ogiso Taro, Shiraki Toshiya, Okajima Kazuto, Tanino Tadatoshi, Iwaki Masahiro, Wada Tetsuyuki
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
J Drug Target. 2002 Aug;10(5):369-78. doi: 10.1080/1061186021000001814.
In order to quantitatively investigate the importance of transfollicular pathway for drug delivery, drug penetration through human scalp skin was investigated using liquid formulations containing lipophilic and hydrophilic drugs in vitro. The penetration pathway for drugs through the scalp skin was examined using fluorescent probes. Additionally, the drug penetration through the scalp skin was compared with that via human abdominal skin to clarify the usefulness of intrafollicular delivery. Lipophilic melatonin (MT) and ketoprofen (KP) showed high permeabilities through the scalp skin, although the flux of KP was much higher. Absorption enhancers, N-methyl-2-pyrrolidone and isopropylmyristate, only slightly increased the fluxes. Hydrophilic fluorouracil (5FU) and acyclovir (ACV) penetrated through the scalp skin with relatively large fluxes. However, there was large variability in the fluxes of these drugs across scalp skin from different sources. When the relationship between the flux and hair follicle density was estimated, there was good correlation between the two (r = 0.651 for MT and r = 0.666 for ACV, P < 0.05). The histologic examination of the scalp skin, following application of the formulation with nile red or sodium fluorescein, indicated that the probes permeated into the junction of the internal and external root sheath of follicles and diffused into the dermis via the outer root sheath at the initial times. The penetration of nile red, a lipophilic probe, via the stratum corneum of scalp skin was later than that via the follicles. The permeation of MT and 5FU through the scalp skin was much higher than that via the abdominal skin, being 27 and 48 times as high as the abdominal skin, respectively. These results indicate that the drug delivery through the scalp skin will offer an available delivery means for drugs, particularly for hydrophilic drugs.
为了定量研究经毛囊途径在药物递送中的重要性，体外使用含有亲脂性和亲水性药物的液体制剂研究了药物透过人头皮皮肤的情况。使用荧光探针检测药物透过头皮皮肤的途径。此外，将药物透过头皮皮肤的情况与经人腹部皮肤的情况进行比较，以阐明毛囊内给药的有效性。亲脂性的褪黑素（MT）和酮洛芬（KP）透过头皮皮肤的渗透率较高，尽管KP的通量要高得多。吸收促进剂N-甲基-2-吡咯烷酮和肉豆蔻酸异丙酯仅略微增加了通量。亲水性的氟尿嘧啶（5FU）和阿昔洛韦（ACV）以相对较大的通量透过头皮皮肤。然而，这些药物在来自不同来源的头皮皮肤中的通量存在很大差异。当估计通量与毛囊密度之间的关系时，两者之间存在良好的相关性（MT的r = 0.651，ACV的r = 0.666，P < 0.05）。在应用含尼罗红或荧光素钠的制剂后，对头皮皮肤进行组织学检查表明，探针在最初阶段渗透到毛囊内外根鞘的交界处，并通过外根鞘扩散到真皮中。亲脂性探针尼罗红透过头皮皮肤角质层的时间比透过毛囊的时间晚。MT和5FU透过头皮皮肤的渗透率远高于透过腹部皮肤的渗透率，分别是腹部皮肤的27倍和48倍。这些结果表明，通过头皮皮肤给药将为药物提供一种可行的给药方式，特别是对于亲水性药物。
