Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers

Several ex vivo and in vitro skin models are available in the toolbox of dermatological and cosmetic research. Some of them are widely used in drug penetration testing. The excised skins show higher variability, while the in vitro skins provide more reproducible data. The aim of the current study wa...

Full description

Bibliographic Details
Main Authors: Dorottya Kocsis, Hichem Kichou, Katalin Döme, Zsófia Varga-Medveczky, Zsolt Révész, Istvan Antal, Franciska Erdő
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/8/1689
_version_ 1827598708171079680
author Dorottya Kocsis
Hichem Kichou
Katalin Döme
Zsófia Varga-Medveczky
Zsolt Révész
Istvan Antal
Franciska Erdő
author_facet Dorottya Kocsis
Hichem Kichou
Katalin Döme
Zsófia Varga-Medveczky
Zsolt Révész
Istvan Antal
Franciska Erdő
author_sort Dorottya Kocsis
collection DOAJ
description Several ex vivo and in vitro skin models are available in the toolbox of dermatological and cosmetic research. Some of them are widely used in drug penetration testing. The excised skins show higher variability, while the in vitro skins provide more reproducible data. The aim of the current study was to compare the chemical composition of different skin models (excised rat skin, excised human skin and human-reconstructed epidermis) by measurement of ceramides, cholesterol, lactate, urea, protein and water at different depths of the tissues. The second goal was to compile a testing system, which includes a skin-on-a-chip diffusion setup and a confocal Raman spectroscopy for testing drug diffusion across the skin barrier and accumulation in the tissue models. A hydrophilic drug caffeine and the P-glycoprotein substrate quinidine were used in the study as topical cream formulations. The results indicate that although the transdermal diffusion of quinidine is lower, the skin accumulation was comparable for the two drugs. The various skin models showed different chemical compositions. The human skin was abundant in ceramides and cholesterol, while the reconstructed skin contained less water and more urea and protein. Based on these results, it can be concluded that skin-on-a-chip and confocal Raman microspectroscopy are suitable for testing drug penetration and distribution at different skin layers within an exposition window. Furthermore, obese human skin should be treated with caution for skin absorption testing due to its unbalanced composition.
first_indexed 2024-03-09T03:57:46Z
format Article
id doaj.art-aa023d8b484e4fe282d507f823e5516c
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-03-09T03:57:46Z
publishDate 2022-08-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-aa023d8b484e4fe282d507f823e5516c2023-12-03T14:17:51ZengMDPI AGPharmaceutics1999-49232022-08-01148168910.3390/pharmaceutics14081689Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion ChambersDorottya Kocsis0Hichem Kichou1Katalin Döme2Zsófia Varga-Medveczky3Zsolt Révész4Istvan Antal5Franciska Erdő6Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, H-1083 Budapest, HungaryEA 6295 Nanomédicaments et NanoSondes (NMNS) Laboratory, University of Tours, 37000 Tours, FranceDepartment of Pharmaceutics, Semmelweis University, H-1092 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, H-1083 Budapest, HungaryRévész Plasztika, H-1125 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, H-1092 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, H-1083 Budapest, HungarySeveral ex vivo and in vitro skin models are available in the toolbox of dermatological and cosmetic research. Some of them are widely used in drug penetration testing. The excised skins show higher variability, while the in vitro skins provide more reproducible data. The aim of the current study was to compare the chemical composition of different skin models (excised rat skin, excised human skin and human-reconstructed epidermis) by measurement of ceramides, cholesterol, lactate, urea, protein and water at different depths of the tissues. The second goal was to compile a testing system, which includes a skin-on-a-chip diffusion setup and a confocal Raman spectroscopy for testing drug diffusion across the skin barrier and accumulation in the tissue models. A hydrophilic drug caffeine and the P-glycoprotein substrate quinidine were used in the study as topical cream formulations. The results indicate that although the transdermal diffusion of quinidine is lower, the skin accumulation was comparable for the two drugs. The various skin models showed different chemical compositions. The human skin was abundant in ceramides and cholesterol, while the reconstructed skin contained less water and more urea and protein. Based on these results, it can be concluded that skin-on-a-chip and confocal Raman microspectroscopy are suitable for testing drug penetration and distribution at different skin layers within an exposition window. Furthermore, obese human skin should be treated with caution for skin absorption testing due to its unbalanced composition.https://www.mdpi.com/1999-4923/14/8/1689skin barriertransdermal deliveryskin penetrationconfocal Raman spectroscopyskin-on-a-chip microfluidic devicehydration
spellingShingle Dorottya Kocsis
Hichem Kichou
Katalin Döme
Zsófia Varga-Medveczky
Zsolt Révész
Istvan Antal
Franciska Erdő
Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
Pharmaceutics
skin barrier
transdermal delivery
skin penetration
confocal Raman spectroscopy
skin-on-a-chip microfluidic device
hydration
title Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
title_full Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
title_fullStr Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
title_full_unstemmed Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
title_short Structural and Functional Analysis of Excised Skins and Human Reconstructed Epidermis with Confocal Raman Spectroscopy and in Microfluidic Diffusion Chambers
title_sort structural and functional analysis of excised skins and human reconstructed epidermis with confocal raman spectroscopy and in microfluidic diffusion chambers
topic skin barrier
transdermal delivery
skin penetration
confocal Raman spectroscopy
skin-on-a-chip microfluidic device
hydration
url https://www.mdpi.com/1999-4923/14/8/1689
work_keys_str_mv AT dorottyakocsis structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT hichemkichou structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT katalindome structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT zsofiavargamedveczky structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT zsoltrevesz structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT istvanantal structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers
AT franciskaerdo structuralandfunctionalanalysisofexcisedskinsandhumanreconstructedepidermiswithconfocalramanspectroscopyandinmicrofluidicdiffusionchambers