Exploring the Surface For Skin Deep Defense

Courtesy Photo | Chemical distribution profiles in stratum corneum (SC) after 15 and 60 min of exposure on normal skin. High concentration of chemical remained in 2 μm thickness to the skin surface within 60 minutes of exposure; no significant difference was determined on surface concentrations and distribution curves for individual chemicals, suggesting the time-limiting diffusion of chemicals in the SC. See additional results for Paraoxon and Butenafine to follow.  

FORT BELVOIR, VA, UNITED STATES

08.22.2017

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

U.S. adversaries have shown little to no hesitation deploying chemical weapons on the battlefield and against civilians. While current protective garments provide warfighters with adequate levels of defense, the possibility still exists that some skin could be exposed, which might lead to fatal contamination. Understanding how these agents are absorbed in the skin is critical to ensuring warfighter safety.

In response to this rising threat, the Defense Threat Reduction Agency’s Chemical and Biological Technologies Department is developing the Toxicant Penetration and Scavenging portfolio. The program, managed by DTRA’s Brian Pate, Ph.D., explores the development of countermeasures, as well as the structural relationships between chemical and biological agents and substrates, to selectively sequester, remove and stop the transport of harmful agents.

One project in the portfolio seeks to understand how chemical agents and surrogates partition into the stratum corneum (SC) of human skin, the body’s largest organ. Recently highlighted in the Applied Toxicology article, “Depth-Dependent Stratum Corneum Permeability in Human Skin In Vitro,”the University of California, San Francisco researchers explore how to prevent skin absorption of chemical agents and effectively decontaminate infected areas. The project utilizes a multifactorial approach in animal and human models in a high-throughput manner.

The SC functions as the first barrier of the human body, protecting against external toxicants and transepidermal water loss. The SC is composed of 10 to 15 cross-linked corneocyte layers embedded in a continuous lipid phase. Corneocytes are flat, dead cells composed of keratin protein, hydrating water and natural moisturizing factors. This unique composition and structural arrangement provides a rate determining membrane for percutaneous penetration. Chemicals can penetrate the SC, affecting molecular diffusion and controlling skin permeability.

A better understanding of chemical absorption and partitioning mechanics in the SC is important for explaining how chemical agents penetrate the skin. This increased understanding will aid researchers in improving decontamination methods for exposed warfighters.

Alteration of the SC’s composition and structure has a significant impact on skin barrier function. Fatty acids influence barrier function through enhancing chemical partitioning into the SC intercellular lipid domain. Exposure of the SC to neutral pH decreases skin barrier homeostasis and SC integrity and cohesion.

Researchers first evaluated in vitro dermatopharmacokinetic profiles of chemicals across the SC using a method that involves repeatedly tape-stripping the chemical dosing site after exposure. This is followed by measuring the chemical concentration and SC thickness on the tape strips.

This novel approach allowed the dermatopharmacokinetic studies of toxic chemicals, such as pesticides and chemical warfare agents, on human skin models. The dermatopharmacokinetic model was established in vivo to assess the rate and extent of a topically applied chemical to reach the circulatory systems.

From this, data analysis derived both partition and diffusion parameters, and researchers evaluated the partition of the chemical between vehicle and SC, as well as the resistance of SC to chemical diffusion.

Researchers also tested paraoxon, a potent acetylcholinesterase-inhibiting pesticide and close simulant to G and V series nerve agents. Model compounds were examined on intact skin at 15 and 60 minutes to examine the stability of their diffusion coefficient over time. The homogeneity of SC for chemical transportation was investigated by comparing the SC distribution profiles and diffusion coefficients obtained from intact and superficial SC-removed skin samples.

By understanding how chemical warfare agents penetrate the skin, the Toxicant Penetration and Scavenging portfolio will advance protections for our warfighters and improve countermeasures.

POC: Brian Pate, Ph.D.; [e-mail]

• Date Taken: 08.22.2017
• Date Posted: 08.22.2017 14:33
• Story ID: 245597
• Location: FORT BELVOIR, VA, US