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Biophysical models for skin transport and absorption.
Dermal absorption and toxicity assessment, 2nd edition. Roberts MS, Walters KA, eds. New York: Informa Healthcare, 2007 Dec; :249-267
Absorption of molecules (applied drugs and chemicals) through the skin proceeds bv sequential diffusion steps through the stratum corneum (SC, barrier), viable epidermal, and dermal layers (1-3). Within each of these strata, absorption involves partitioning into and diffusion within several components of an inherently heterogeneous microstructure, and in the dermis it is accompanied by clearance into the systemic circulation via the dermal vasculature. Microscopic theoretical models of these transport processes have evolved to the point where they can often yield mechanistic understanding and reasonable quantitative predictions of transdermal transport rates, subsurface concentration levels, and rates of vascular clearance. Such models--and the understanding they carry with them--are playing a growing role in the areas of topical and transdermally delivered drug development (4-6) and risk assessment of chemical exposure (7- 10). Their importance in the first area is underscored by the facts that" overcoming the skin barrier in a safe and effective way still remains the bottleneck of transdermal and topical therapies" (11), and that "the transdermal route now vies with oral treatment as the most successful innovative research area in drug delivery, with around 40% of drug delivery candidate products under clinical evaluation related to transdermal or dermal systems" (12). Direct relevance of biophysical models to risk assessment is also high because the number of chemicals to which the population is exposed on a daily basis far exceeds the small fraction thereof that could ever be studied experimentally. For the remaining compounds (the vast majority), judicious application of well-conceived mathematical models can make the difference between a plausible and defensible risk analysis and the lack thereof. Both areas furnish strong motivation to understand how microscopic physiological structure and heterogeneity govern penetration.
Skin-exposure; Skin-absorption; Absorption-rates; Chemical-kinetics; Chemical-properties; Dermatology; Models; Drugs; Drug-therapy; Physiological-factors; Physiological-effects; Physiological-response
Dermal absorption and toxicity assessment, 2nd edition
University of Cincinnati