A water gradient can be used to regulate drug transport across skin.
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.
Björklund
Sebastian
S
Division of Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100 Lund, Sweden. Sebastian.Bjorklund@fkem1.lu.se
Engblom
Johan
J
Thuresson
Krister
K
Sparr
Emma
E
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D004058:Diffusion; D008795:Metronidazole / Q000493:pharmacokinetics*; D012459:Salicylates / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014867:Water / Q000378:metabolism*
D000890:Anti-Infective Agents; D012459:Salicylates; D014867:Water; D008795:Metronidazole; C033069:methyl salicylate