The skin is a multifunctional and multicompartment organ. Figure 65–1 outlines general features of skin structure and percutaneous absorption pathways. Drugs can be applied to skin for 2 purposes: to directly treat disorders of the skin and to deliver drugs to other tissues.
Cutaneous drug delivery. Diagrammatic representation of the 3 compartments of the skin as they relate to drug delivery: surface, stratum (Str.), and viable tissues. After application of a drug to the surface, evaporation and structural/compositional alterations occur that determine the drug's bioavailability. 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, and thence to internal cells and organs. (Reproduced with permission from Wolff K, et al., eds. Fitzpatrick's Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008, Figure 215–1. Copyright © 2008 by The McGraw-Hill Companies, Inc. All rights reserved.)
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.
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. Many drugs may partition into the stratum corneum and form a reservoir that will diffuse into the rest of skin even after topical application of the drug has ceased. The stratum corneum differs in thickness, with the palm and sole being the thickest (400-600 μm) followed by the general body stratum corneum (10-16 μm), and the scrotum (5 μm). Facial and post-auricular regions have the thinnest stratum corneum.
Living Epidermis. The living layers of the epidermis with metabolically active cells comprise a layer ~100 μm thick (Figure 65–2). Intercalated in the living epidermis are pigment-producing cells (melanocytes), dendritic antigen-presenting cells (Langerhans cells), and other immune cells (γ-δ T-cells); in diseased epidermis, many immunological cells, including lymphocytes and polymorphonuclear leucocytes, may be present and be directly affected by applied drugs.
Structure of the epidermis. The epidermis matures progressively from the stratum basale (SB) to the stratum spinosum (SS), stratum granulosum (SG), and stratum corneum (SC). Important structural and metabolic proteins are produced at specific layers of the epidermis. (Reproduced with permission from Wolff K, et al., eds. Fitzpatrick's Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008, Figure 45–2. Copyright © 2008 ...