Exploring the Depths of Percutaneous Penetration

By: Elsa Jungman, Université Paris-Sud

Posted: July 3, 2012

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Scheuplein stated, “To increase penetration, [use] a solvent with the opposite lipophilicity.” He proposed in 1971 a stratum corneum diffusion model that would be related mainly to transcellular diffusion with parallel pathways. Bound water in the keratinocytes provides the primary diffusion resistance. It was not until the 1990s that the first semi-empirical predictive model appeared by Potts and Guy, based on the molecular weight and partition coefficient of the molecule.

The day’s sessions ended with a pleasant dinner and a closing speech by Keith Brain, University of Cardiff.

Nailing Down Nails

On the final day, the morning was focused on nail permeation. Stuart Jones, King’s College, London, explained how the nail is a rich keratin barrier and that 80% of the keratin found in the nail is a hard, hair type of keratin; the remaining 20% is a soft, skin type keratin. This combination gives a rigid structure that is difficult to penetrate, including with drugs, to treat nail diseases. The penetration lag time can last hours but one approach to improve this penetration rate is to manipulate the keratin structure.

The nail environment is different from the skin in that the nail has the ability to be charged, and charged molecules make molecular interactions possible. Four categories of interactions can be developed for improving the drug permeation through the nail. First are solvent-barrier interactions, for example an alcohol-water mixture, which can enhance diffusion; a change of viscosity does not affect water flux. Second are drug-solvent interactions, as supramolecular structures can modify ungual diffusion. Third are drug ion pairs, ions and complexes, which can modify diffusion. Finally, drug-drug interactions; dimer forms have the potential to modify ungual diffusion. This could be a key function; however, it is only in the early stages of development.