Factors Influencing Expression and Specificity of Carboxylesterases in Skin: Implications for Local and Systemic Paraben Ester Toxicity

Carboxylesterases (CES) are present in a number of skin cells and have known physiological and exogenous substrates including drugs, chemicals, pro-drugs, carbamate and pyrethroid insecticides, cosmetic chemicals and environmental toxicants. A typical reaction scheme for CES is presented in Figure 1. During drug discovery and design, an ester linkage is frequently included to selectively target a pro-drug to a tissue or to improve dermal absorption and deliver a novel compound. Skin is an important tissue regulating uptake of environmental chemicals as well as a delivery site for drugs targeted locally to the skin and systemically.