A novel diffusion model describing the absorption of chemicals through complex biological membranes

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PI: Deon van der Merwe (VetMed); co-PI: Caterina Scoglio (ECE); student: Phillip Schumm (ECE).


Abstract

Our skin is the point of contact between our bodies and a multitude of xenobiotic chemicals in our environment. The large surface area and accessibility of the skin not only makes it vulnerable to toxic chemicals, but also makes it a convenient site for the application of pharmaceuticals and cosmetics. The effects that these chemicals may have, whether it be toxic effects or beneficial effects, depend on the degree to which they are absorbed into the body. The skin is a highly complex biological membrane that evolved to protect us from excessive water loss and fluctuations in external temperature. It also serves as a barrier to mechanical and chemical insults. Most of the barrier properties of the skin depend on the outer skin layer, called the stratum corneum. The stratum corneum consists of layers of keratinized cells embedded in a semi-crystalline, layered lipid matrix. The lipid matrix is the most important route of absorption through the skin for most chemicals. Current models view the lipid matrix as a homogenous medium through which chemicals diffuse passively from high to low concentration according Fick’s first law of diffusion. This model predicts that the fraction of a chemical that is absorbed through the skin over a specified period of time is constant, and will remain constant at various concentrations of chemical applied to the skin surface. It also predicts that chemicals will spread through the lipid matrix in a smooth continuum from high to low concentration. Both of these predictions are contradicted by experimental evidence. The fraction of the applied dose of a chemical that is absorbed per unit of time diminishes as the dose concentration is increased; and chemicals tend to penetrate the lipid matrix in an irregular pattern, concentrating in some areas of the lipid matrix, while being present at much lower concentrations in other areas. We propose an alternative model for describing chemical movement in the stratum corneum lipid matrix based on successive partitioning through multiple compartments that describe the physical-chemical characteristics of the lipid matrix. This model offers the opportunity to describe the absorption of chemicals through skin in a manner that closely resembles actual diffusion processes and experimental results.


Publications

P. Schumm, C. Scoglio, D. van der Merwe

"A network model of successive partitioning-limited solute diffusion through the stratum corneum"

Journal of Theoretical Biology, Volume 262, Issue 3, 7 February 2010, Pages 471-477.


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