A novel approach to modelling water transport and drug diffusion through the stratum corneum

<p>Abstract</p> <p>Background</p> <p>The potential of using skin as an alternative path for systemically administering active drugs has attracted considerable interest, since the creation of novel drugs capable of diffusing through the skin would provide a great step towards easily applicable -and more humane- therapeutic solutions. However, for drugs to be able to diffuse, they necessarily have to cross a permeability barrier: the <it>stratum corneum </it>(SC), the uppermost set of skin layers. The precise mechanism by which drugs penetrate the skin is generally thought to be diffusion of molecules through this set of layers following a "tortuous pathway" around corneocytes, i.e. impermeable dead cells.</p> <p>Results</p> <p>In this work, we simulate water transport and drug diffusion using a three-dimensional porous media model. Our numerical simulations show that diffusion takes place through the SC regardless of the direction and magnitude of the fluid pressure gradient, while the magnitude of the concentrations calculated are consistent with experimental studies.</p> <p>Conclusions</p> <p>Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties.</p

Porous medium mechanics and the skin barrier

A skin-air model is developed to predict changes in transepidermal water loss following changes in ambient relative humidity and following minute damages to the skin. In vivo experiments on human subjects are used to validate the model

Do osmotic forces play a role in the uptake of water by human skin ?

Background/purpose: To describe the water and ion transport through the skin under different conditions, we developed a three-component mixture model. This model has proven to describe the transient change in transepidermal water loss (TEWL) after a change in relative humidity and the result of damage to the skin. Osmotic forces arc present in the model. To assess the influence of osmotic forces on the water uptake of the skin, we investigated transient TEWL values after 1 h application of salt solutions of different molarities (0, 1, and 4 M NaCl). Methods: Filters saturated with 0, 1, and 4 M NaCl solution were applied for 1 h under occlusion. TEWL was measured 50–90 min after removal of the solution. The transient water loss curves were fit with an exponential function. The area under the fitted curve was calculated and regarded as a measure for the amount of extra water absorbed in the skin. Results: For all molarities, TEWL is increased immediately after removal of the solution. In time, this increase decays until pre-application values are reached again. The rate of decrease differs significantly for all three molarities. Ninety-five per cent of the increase has been reversed after 30, 19, and 6 min for the 0, 1, and 4 M case, respectively. The amount of water absorbed differs significantly between the three molarities 7.3±2.0; 3.9±1.0; 2.0±0.5 g/m2, respectively. Conclusions: In all cases, there was an increase in TEWL immediately after removal of the solution. The significant differences in decay time and amount of water absorbed between the three molarities indicate that osmotic forces do play an important role in the water uptake