Morphologic basis for a pore-pathway in mammalian stratum corneum

Area of Science:

• Dermatology and skin barrier research.
• Materials science and nanotechnology.
• Pharmacokinetics and drug delivery.

Background:

• The stratum corneum (SC) acts as a primary barrier against external agents.
• Previous studies suggested paracellular routes for SC penetration, but the specific pathway remained unclear.
• Understanding SC penetration is crucial for topical drug delivery and cosmetic formulation.

Purpose of the Study:

• To elucidate the precise in vivo pathway for polar and nonpolar molecule penetration across the murine stratum corneum.
• To investigate how various permeation enhancement techniques affect the SC pathway.
• To identify the structural components within the SC responsible for molecule transport.

Main Methods:

• In vivo application of hydrophilic and hydrophobic tracers to murine skin.
• Utilized various permeation enhancement methods: occlusion, vehicle enhancers, lipid synthesis inhibition, sonophoresis, and iontophoresis.
• Employed advanced electron microscopy techniques for pathway visualization: ruthenium tetroxide, ruthenium red plus osmium tetroxide, osmium vapor precipitation, and microwave postfixation.

Main Results:

• Tracers consistently localized to discrete lacunar domains within the SC's extracellular lamellar membrane system.
• This localization occurred irrespective of tracer polarity or the enhancement method used.
• Lacunar domains, initially discontinuous under basal conditions, showed increased structural continuity upon permeation enhancement.

Conclusions:

• Extracellular lacunar domains represent a distinct pore pathway for both polar and nonpolar molecule penetration across the stratum corneum.
• These lacunar domains are a key structural feature governing SC permeability.
• The findings provide critical insights into the SC barrier function and offer potential targets for modulating skin penetration.