The nanoscopic molecular pathway through human skin

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 7; pp. 1226 - 1233
• Main Authors: Iachina, I., Antonescu, I.E., Dreier, J., Sørensen, J.A., Brewer, J.R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2019
• Subjects: Fluorescence Resonance Energy Transfer; Förster resonance energy transfer; Humans; Lipid Bilayers - metabolism; Skin - metabolism; Skin Absorption; Skin barrier; STED; Super resolution optical microscopy; Transdermal drug delivery; Transdermal drug delivery; Super resolution optical microscopy; Förster resonance energy transfer; Skin barrier; STED
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2019.04.012

Knowledge regarding the barrier properties of human skin is important for understanding skin pathology, developing of transdermal drug delivery systems and computational skin absorption models; however, the molecular pathways through human skin remains to be fully investigated on a nanoscopic level. In particular the nanoscopic pathway of molecules passing the intercellular lipid bilayers separating the corneocytes in the stratum corneum (SC) is not fully elucidated.
Using stimulated emission depletion microscopy (STED) and Förster resonance energy transfer (FRET) the molecular pathways through the SC, the main barrier of the skin, are determined for lipophilic and water-soluble molecules at a nanoscopic resolution.
Using STED and confocal microscopy, water-soluble dyes, were observed to be present in both the corneocytes and in the intercellular lipid matrix, whereas the lipophilic dyes were predominately in the intercellular lipid bilayers. FRET was observed in the SC between the lipophilic and water-soluble dyes, the existence of a minimum possible distance between acceptor and donor molecules of 4.0 ± 0.1 nm was found.
The results indicate that lipophilic molecules penetrate the stratum corneum via the intercellular lipids bilayers separating the corneocytes in the SC, while the more water-soluble molecules penetrate the stratum corneum via the transcellular route through the corneocytes and intercellular lipid bilayers via the polar head groups of lipid molecules in the bilayers.
Knowledge of the nanoscopic molecular pathways through human skin will help understand the skin barrier function and will be of use for computational skin absorption models and transdermal drug delivery strategies.
•Super resolution optical microscopy resolves the intercellular lipid matrix.•FRET was observed between lipophilic and water-soluble dyes in the intercellular lipid matrix.•In SC a minimum distance between lipophilic and water-soluble molecules of 4.0 nm was found.•Water-soluble molecules can move through the intercellular lipid matrix via the polar head groups.