Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F15%3A10312576" target="_blank" >RIV/00216208:11160/15:10312576 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/15:33156524

Výsledek na webu

<a href="http://pubs.acs.org/doi/10.1021/acs.jpcb.5b05522" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.jpcb.5b05522</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.5b05522" target="_blank" >10.1021/acs.jpcb.5b05522</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails

Popis výsledku v původním jazyce

Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight-carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, Which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.

Název v anglickém jazyce

Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails

Popis výsledku anglicky

Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (four- to eight-carbon acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as that of ceramides from healthy skin (24 carbons long on average). Here we address the extent to which the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data. As a result, we observed the same bell-shaped permeability trend for water that was observed in the skin and multilayer membrane experiments for model compounds We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their headgroup conformation because of their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, Which further led to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure, including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

119

Číslo periodika v rámci svazku

30

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

9811-9819

Kód UT WoS článku

000359031400034

EID výsledku v databázi Scopus

2-s2.0-84938254553