title: The potential of metabolic interventions to enhance transdermal drug delivery.
abstract: The stratum corneum is a complex tissue that is metabolically active, and undergoes dynamic structural modifications due to the presence of several self-regulating enzymatic systems. A large number of defensive (protective) functions are embodied in this tissue, each with its own structural and biochemical basis. Moreover, the stratum corneum is responsive to external perturbations to the permeability barrier, upregulating a variety of metabolic processes aimed at restoring normal barrier function. Traditional drug delivery methods, which are of limited effectiveness, view the stratum corneum as a static, but semipermeable membrane. In contrast, newer metabolically based methods, which can be deployed alone, or in conjunction with standard methods, have been shown to expand the spectrum of drugs that can be delivered transdermally in hairless mouse epidermis. Yet, while these new approaches hold great promise, if equally effective in human skin, they pose new questions about the risks of a highly permeabilized stratum corneum.
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, Department of Dermatology and Medicine, University of California San Francisco, California 94121, USA. eliaspm@itsa.ucsf.edu
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Janice
authors.initials: J
authors.lastname: Tsai
authors.forename: Gopinathan K
authors.initials: GK
authors.lastname: Menon
authors.forename: Walter M
authors.initials: WM
authors.lastname: Holleran
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000143:Acids / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D010539:Permeability
chemical_list: D000143:Acids