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The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression
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The nanoscopic molecular pathway through human skin.

I Iachina1, I E Antonescu1, J Dreier2

  • 1Department of Biochemistry and Molecular Biology, University of Southern Denmark, Denmark.

Biochimica Et Biophysica Acta. General Subjects
|April 19, 2019
PubMed
Summary

This study reveals how molecules navigate the skin barrier at the nanoscale. Lipophilic molecules use intercellular lipid bilayers, while water-soluble molecules pass through corneocytes and lipid bilayers for better transdermal drug delivery.

Keywords:
Förster resonance energy transferSTEDSkin barrierSuper resolution optical microscopyTransdermal drug delivery

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Area of Science:

  • Biophysics
  • Dermatology
  • Materials Science

Background:

  • Understanding human skin barrier properties is crucial for pathology and transdermal drug delivery.
  • The nanoscopic molecular pathways through the stratum corneum (SC) remain incompletely understood.
  • Investigating intercellular lipid bilayers is key to elucidating skin penetration.

Purpose of the Study:

  • To determine the nanoscopic molecular pathways of lipophilic and water-soluble molecules through the human skin SC.
  • To elucidate the role of intercellular lipid bilayers in skin penetration.
  • To provide insights for computational skin absorption models and transdermal drug delivery.

Main Methods:

  • Utilized stimulated emission depletion (STED) microscopy for nanoscopic resolution.
  • Employed Förster resonance energy transfer (FRET) to study molecular interactions.
  • Observed the distribution and pathways of lipophilic and water-soluble dyes within the SC.

Main Results:

  • Water-soluble dyes were found in corneocytes and intercellular lipid matrix.
  • Lipophilic dyes predominantly localized within intercellular lipid bilayers.
  • FRET analysis indicated a minimum molecular distance of 4.0 ± 0.1 nm in the SC.

Conclusions:

  • Lipophilic molecules penetrate the SC via intercellular lipid bilayers.
  • Water-soluble molecules utilize a transcellular route, passing through corneocytes and lipid bilayers.
  • Findings enhance understanding of skin barrier function and inform drug delivery strategies.