title: First-principles, structure-based transdermal transport model to evaluate lipid partition and diffusion coefficients of hydrophobic permeants solely from stratum corneum permeation experiments.
abstract: To account for the effect of branched, parallel transport pathways in the intercellular domain of the stratum corneum (SC) on the passive transdermal transport of hydrophobic permeants, we have developed, from first-principles, a new theoretical model-the Two-Tortuosity Model. This new model requires two tortuosity factors to account for: (1) the effective diffusion path length, and (2) the total volume of the branched, parallel transport pathways present in the SC intercellular domain, both of which may be evaluated from known values of the SC structure. After validating the Two-Tortuosity model with simulated SC diffusion experiments in FEMLAB (a finite element software package), the vehicle-bilayer partition coefficient, K(b), and the lipid bilayer diffusion coefficient, D(b), in untreated human SC were evaluated using this new model for two hydrophobic permeants, naphthol (K(b) = 225 +/- 42, D(b) = 1.7 x 10(-7) +/- 0.3 x 10(-7) cm(2)/s) and testosterone (K(b) = 92 +/- 29, D(b) = 1.9 x 10(-8) +/- 0.5 x 10(-8) cm(2)/s). The results presented in this paper demonstrate that this new method to evaluate K(b) and D(b) is comparable to, and simpler than, previous methods, in which SC permeation experiments were combined with octanol-water partition experiments, or with SC solute release experiments, to evaluate K(b) and D(b).
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors: Joseph
authors: J
authors: Kushner
authors: William
authors: W
authors: Deen
authors: Daniel
authors: D
authors: Blankschtein
authors: Robert
authors: R
authors: Langer
mesh_terms: D000279:Administration, Cutaneous; D003198:Computer Simulation; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D020342:Finite Element Analysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D015394:Molecular Structure; D009284:Naphthols / Q000378:metabolism; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013739:Testosterone / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D009284:Naphthols; D004364:Pharmaceutical Preparations; D013739:Testosterone