Hafeez Farhaan, Maibach Howard
Department of Dermatology, University of California, San Francisco, CA 94143-0989, USA.
Cutan Ocul Toxicol. 2013 Oct;32(4):299-303. doi: 10.3109/15569527.2013.780180. Epub 2013 Mar 27.
Skin occlusion influences percutaneous penetration by limiting penetrant evaporation, but also through impeding loss of water from skin and increasing the hydration state of the stratum corneum, thus dramatically altering the physiological nature of the stratum corneum. In general, occlusion is widely utilized to enhance penetration of applied drugs in clinical practice; however, occlusion does not increase the percutaneous absorption of all chemicals.
We focus on what effect occlusion has on the in vitro percutaneous absorption of compounds of varying lipophilicities/hydrophilicities.
Studies and prior reviews of the effects of occlusion on the in vitro percutaneous penetration of penetrants of varying lipophilicities/hydrophilicities were identified in the MEDLINE, PubMED, Embase and Science Citation Index databases using the terms occlusive, occluded, occlusion, in vitro, skin and percutaneous absorption/penetration to generate as broad of a search as possible. From the results generated, abstracts were subsequently scrutinized to identify articles dealing primarily with in vitro models of the skin involving occlusion. Moreover, after the identification of relevant articles, their references were examined to find additional sources of information.
After examining the research articles generated by the search results, five original research articles were obtained that used in vitro occlusion models and provided insight regarding the role of partition coefficients in predicting occlusion's effects on percutaneous penetration; articles that dealt with occlusion and percutaneous penetration but did not shed light on how the lipophilicity/hydrophilicity of a compound could affect occlusion efficacy were excluded. Some of the studies bolster the notion that occlusion-enhanced hydration of the stratum corneum increases the percutaneous absorption of lipophilic molecules more than hydrophilic molecules, which seems to confirm some in vivo studies. However, this effect was not consistent; many studies reviewed did not find that the penetrant's liphophilicity/hydrophilicity reliably predicted occlusion's effect on penetration. In these studies, lipophilic compounds did not demonstrate increased percutaneous absorption under occlusion.
Thus, it does not seem that partition coefficients can reliably predict the effect of occlusion on percutaneous penetration in vitro. This suggests skin occlusion may be more complex than previously thought.
皮肤封闭通过限制渗透剂蒸发来影响经皮渗透，但也通过阻止皮肤水分流失和增加角质层的水合状态来实现，从而显著改变角质层的生理性质。一般来说，在临床实践中，封闭被广泛用于增强外用药物的渗透；然而，封闭并不会增加所有化学物质的经皮吸收。
我们关注封闭对不同亲脂性/亲水性化合物体外经皮吸收的影响。
在MEDLINE、PubMED、Embase和科学引文索引数据库中，使用“封闭的”“被封闭的”“封闭”“体外”“皮肤”和“经皮吸收/渗透”等术语进行检索，以尽可能广泛地搜索关于封闭对不同亲脂性/亲水性渗透剂体外经皮渗透影响的研究和先前的综述。从检索结果中，随后仔细审查摘要，以识别主要涉及皮肤体外模型且涉及封闭的文章。此外，在识别出相关文章后，检查其参考文献以找到更多信息来源。
在检查搜索结果产生的研究文章后，获得了五篇原始研究文章，这些文章使用了体外封闭模型，并提供了关于分配系数在预测封闭对经皮渗透影响方面作用的见解；那些涉及封闭和经皮渗透但未阐明化合物的亲脂性/亲水性如何影响封闭效果的文章被排除。一些研究支持这样的观点，即封闭增强的角质层水合作用增加亲脂性分子的经皮吸收比亲水性分子更多，这似乎证实了一些体内研究。然而，这种效果并不一致；许多综述的研究没有发现渗透剂的亲脂性/亲水性能够可靠地预测封闭对渗透的影响。在这些研究中，亲脂性化合物在封闭条件下并未表现出经皮吸收增加。
因此，分配系数似乎不能可靠地预测封闭对体外经皮渗透的影响。这表明皮肤封闭可能比以前认为的更为复杂。
