Characterization of Water and a Model Lipophilic Compound in Human Stratum Corneum by NMR Spectroscopy and Equilibrium Sorption.
The stratum corneum (SC) is the outermost skin layer in humans and other mammals and the primary barrier to water loss and environmental exposure to chemicals and microorganisms. It consists of flattened, keratin-filled corneocytes surrounded by well-organized lipid layers. Human SC at varying degrees of hydration with and without addition of a model lipophilic compound, 2-(trifluoromethyl) benzonitrile (TFMB), was studied using proton (1H) and fluorine (19F) nuclear magnetic resonance techniques. Proton spectral analyses revealed that water mainly occupies the corneocytes in agreement with prior studies. Observations from19F spectral and spin-lattice relaxation time (T1) analyses showed that TFMB is primarily present in the lipids with small amounts in water, which is located within the corneocytes. This is consistent with TFMB sorption, which was measured in SC with and without lipid extraction. The presence of TFMB within the corneocytes supports the hypothesis that transcellular diffusion of a lipophilic compound like TFMB may contribute to SC permeation.
Chemical and Biological Engineering Department, Colorado School of Mines, Golden, Colorado 80401; Department of Psychological and Brain Sciences and Dartmouth Brain Imaging Center, Dartmouth College, Hanover, New Hampshire 03755.
Chandana
C
Kodiweera
Chemical and Biological Engineering Department, Colorado School of Mines, Golden, Colorado 80401.
Wayne J
WJ
Romonchuk
Department of Chemistry, Colorado School of Mines, Golden, Colorado 80401.
Yuan
Y
Yang
Chemical and Biological Engineering Department, Colorado School of Mines, Golden, Colorado 80401. Electronic address: abunge@mines.edu.
Annette L
AL
Bunge
D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000493:pharmacokinetics* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D014050:Toluene / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D008055:Lipids; D014867:Water; D014050:Toluene; C069976:2-trifluoromethylbenzoic acid
NMR spectroscopy; chemical pathways; corneocytes; extracellular lipid; human stratum corneum (SC); lipophilic chemicals; partition coefficient; skin; sorption; spin-lattice relaxation time; transdermal drug delivery