ABSTRACT

Corneum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 24.3 Epidermal Biochemical Differentiation: Phospholipids to Metabolites . . . . . . . . . . . . . . . . . . 300 24.4 Biological Efficacy of Phospholipid Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 24.5 Topical Application of Phosphatidylcholine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 24.6 Phosphatidylcholine as an Active Drug Substance and as a Structure-Forming “Inert”

Excipient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 24.7 Effects of the Topical Application of Fluid-State Phosphatidylcholine . . . . . . . . . . . . . . . . . . 303 24.8 Effects of Fluid-State PC Matrix Loaded with Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 24.9 Effects of Topical Application of Gel-State PCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 24.10 Uptake and Tolerance Gel-State PCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 24.11 Effects of the Topical Application of a Gel-State PC Matrix Loaded with

Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 24.12 Effects of the Topical Application of Gel-State PC Matrix Loaded with Phospholipid

Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 24.13 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307

It is now generally accepted that stratum corneum as the uppermost layer of the skin is a biosensor that regulates metabolic responses of the skin to the changes in the environment.1 Variations in environmental humidity affect the rate of the permeability barrier synthesis. The chain of events involved in this response includes (1) detection of a change in skin hydration (e.g., due to increased transepidermal water loss), (2) activation of a variety of enzymes including phospholipase D (PLD), and (3) modulation of the rate of the pro-barrier to barrier lipid transformation.2 In this chain of events, PLD not only controls the rate of lipid transformation, but is also involved in the release of water-soluble metabolites, which function as organic osmolytes3 and at the same time exert their biological protective activity.4,5 These metabolites play an essential role in the maintenance of a balanced skin hydration.