Computational Modelling of Transdermal Drug Delivery
Many medicinal compounds cannot be delivered orally because they are degraded in the intestine or by the liver, are poorly absorbed, or irritate the gastrointestinal tract. In such cases, transdermal delivery may be considered. However, skin is not uniform between genders, age, race, and even on the same person. A model membrane is often used to minimise these differences, although experimentally this is still time-consuming.
The use of computational analysis to compare existing data between human skin and model membranes not only shows how effective a given model membrane is, but also can explain why some small molecules can cross the skin barrier more easily than others. It can also explain the mechanism behind permeation.
In a related research area, data from the water/octanol partition coefficient, expressed in the form log P, has been used to predict the capability of organic molecules to transfer across membranes. Our interest in this and other physicochemical model systems covers measurement methods, limitations of the log P model, alternatives to log P and its use in prediction through the quantitative structure-activity relationship (QSAR) analyses.
In particular, we are looking at how measurements involving the water/octanol system can shed light on biologically important solvation and de-solvation processes. The aim is to investigate the transfer of small organic molecules, not only from aqueous solution to membranes, but also to other hydrophobic environments such as “hydrophobic” binding sites on proteins.
Publications
Lansdell-Smith, P. H., Mitchell, J. C., and Hyde, R. M. (2005) Correlation of permeability through skin and a model PDMS membrane. British Pharmaceutical Conference, Manchester UK, September, 2005. Journal of Pharmacy and Pharmacology, 57. ISSN 0022-3573.