Shutdown and Recovery of the Barrier Function of Human Skin

Project Description

This project is designed to discover how surfactants, such as detergents or emulsifiers, control the permeation of chemical compounds into human skin. Do surfactants only change the stability of the molecules of the outer layer, or do they also form larger objects capable of carrying other chemicals? Harmful chemicals in solid or liquid form, as well as pathogens such as viruses or bacteria, are usually stopped at the stratum corneum from entering the human body. However, some molecules can cross this barrier fairly unhindered and be found within the bloodstream hours after their first contact with human skin. The small molecules best known to possess this ability can be as diverse as steroid hormones, nicotine, certain analgesics, and even chemical warfare agents (Sarin, VX). To safely develop more advanced materials, it is also necessary to reveal the hidden pathways used by these molecules, either individually or with assistance from surfactants. We intend to study the permeation into skin of vesicles and micelles made by lipids and surfactant molecules, along and across the layers of the stratum corneum’s lipid matrix Our strategy is twofold: (1) we will quantify, both in solution and within the stratum corneum, the relative equilibria among phospholipids, added surfactants such as olysorbate, and cofactors such as testosterone; and (2) we will compare the rates of permeation of individual lipids and surfactants under the two alternative hypotheses that a molecule can either travel while embedded in a vesicle or micelle, or individually by migrating into the stratum orneum lipid matrix. This study is likely to transform several years of fundamental research into novel predictive tools, allowing one to manipulate the skin’s barrier function in ways that preserve and even promote the health of individuals that come in contact with new materials or formulations.