The nanoscopic molecular pathway through human skin

I. Iachina, I. E. Antonescu, J. Dreier, J. A. Sørensen, J. R. Brewer*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: 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. Methods: 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. Results: 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. Conclusions: 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. General significance: 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.

OriginalsprogEngelsk
TidsskriftBiochimica et Biophysica Acta - General Subjects
Vol/bind1863
Udgave nummer7
Sider (fra-til)1226-1233
ISSN0304-4165
DOI
StatusUdgivet - 1. jul. 2019

Fingeraftryk

Skin
Lipid Bilayers
Lipid bilayers
Molecules
Skin Absorption
Coloring Agents
Stimulated emission
Water
Microscopy
Energy transfer
Lipids
Microscopic examination
Confocal Microscopy
Confocal microscopy
Pathology
Drug delivery
Pharmaceutical Preparations

Citer dette

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title = "The nanoscopic molecular pathway through human skin",
abstract = "Background: 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. Methods: Using stimulated emission depletion microscopy (STED) and F{\"o}rster 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. Results: 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. Conclusions: 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. General significance: 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.",
keywords = "F{\"o}rster resonance energy transfer, Skin barrier, STED, Super resolution optical microscopy, Transdermal drug delivery",
author = "I. Iachina and Antonescu, {I. E.} and J. Dreier and S{\o}rensen, {J. A.} and Brewer, {J. R.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.bbagen.2019.04.012",
language = "English",
volume = "1863",
pages = "1226--1233",
journal = "B B A - General Subjects",
issn = "0304-4165",
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}

The nanoscopic molecular pathway through human skin. / Iachina, I.; Antonescu, I. E.; Dreier, J.; Sørensen, J. A.; Brewer, J. R.

I: Biochimica et Biophysica Acta - General Subjects, Bind 1863, Nr. 7, 01.07.2019, s. 1226-1233.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The nanoscopic molecular pathway through human skin

AU - Iachina, I.

AU - Antonescu, I. E.

AU - Dreier, J.

AU - Sørensen, J. A.

AU - Brewer, J. R.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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. General significance: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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. General significance: 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.

KW - Förster resonance energy transfer

KW - Skin barrier

KW - STED

KW - Super resolution optical microscopy

KW - Transdermal drug delivery

U2 - 10.1016/j.bbagen.2019.04.012

DO - 10.1016/j.bbagen.2019.04.012

M3 - Journal article

C2 - 30998962

AN - SCOPUS:85065091274

VL - 1863

SP - 1226

EP - 1233

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 7

ER -