期刊
JOURNAL OF CONTROLLED RELEASE
卷 143, 期 2, 页码 191-200出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2010.01.005
关键词
Diffusive transport; Flow-through cell; Osmotic gradient; Responding membrane; Stratum corneum; Transdermal drug delivery
资金
- Research School in Pharmaceutical Sciences (FLAK)
- Gustaf Th Ohlssons Foundation (Stiftelsen Gustaf Th Ohlssons Fond)
- Swedish Foundation for Strategic Research (Stiftelsen for Strategisk Forskning)
- Swedish Research Council (Vetenskapsradet)
- Linneaus programme
At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the outside of skin and changes in this gradient may affect its structure and function. In this study we raise the question: How do changes in the water gradient across skin affect its permeability? We approach this problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown that the transport of metronidazole (log P-o/w=0.0) and methyl salicylate (log P-o/w=2.5) across skin increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the boundary conditions of the water gradient needed to make use of this effect. (C) 2010 Elsevier B.V. All rights reserved.
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