Drugs can be applied to skin for two purposes: to directly treat disorders of the skin and to deliver drugs to other tissues (Figure 65–1). The optimization of cutaneous therapies requires detailed physiological knowledge of the skin as reviewed extensively elsewhere (Wolff et al., 2008). This chapter emphasizes the basis of common skin therapies. Therapies that are used primarily for skin diseases are discussed in detail; other therapies that are applicable for skin disease are summarized and the reader referred to the appropriate portion of this book for their detailed pharmacology and toxicology.
Cutaneous drug delivery. Diagrammatic representation of the three compartments of the skin as they relate to drug delivery: surface, stratum (Str.), and viable tissues. After application of drugs to the surface, evaporation, structural, and compositional alterations, which determine the bioavailability of drugs, occur in the applied formulation. The stratum corneum limits diffusion of compounds into the viable skin and body. After absorption, compounds either bind targets in viable tissues or diffuse within the viable tissue or into the cutaneous vasculature, where they may be carried to internal cells and organs. (Reproduced with permission from Wolff et al., 2008. Figure 215-1. Copyright © The McGraw-Hill Companies, Inc. All rights reserved. Available at http://www.accessmedicine.com.)
Many skin diseases can be treated with active pharmacological agents topically; understanding the principles for percutaneous drug absorption and metabolism are essential for their effective and safe use.
Non-pharmacological therapy for skin diseases includes the entire electromagnetic spectrum applied by many sources, such as lasers, X-rays, visible light, and infrared light. These approaches may be used alone or to enhance the penetration or alter the nature of drugs and prodrugs. Freezing and ultrasound are other physical therapies that alter epidermal structure for direct treatment or to enhance percutaneous absorption of drugs. Chemicals are used to decrease the effect of various wavelengths of ultraviolet (UV) light and ionizing radiation.
Effective and safe use of topical agents requires appreciation of the physical and physiological variables that influence the interactions of drugs and the skin, impacting absorption and transport. The skin is a multifunctional and multicompartment organ affected in numerous ways by diseases and their treatments. Figure 65–1 outlines general features of skin structure and percutaneous absorption pathways. The bulk of percutaneous absorption for most agents is through the stratum corneum, which covers almost the entire skin surface. Epidermal structure and the role of hair follicles and sweat glands as pathways for absorption are reviewed below.
Stratum Corneum. The stratum corneum (outer 5-600 μm) is the major barrier to percutaneous absorption of drugs and to the loss of water from the body. It is made of "dead" epidermal cells that cannot reproduce and have lost their nuclei and mitochondria. It possesses multiple proteins and lipids ...