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Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device

The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug...

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Autores principales: Bajza, Ágnes, Kocsis, Dorottya, Berezvai, Orsolya, Laki, András József, Lukács, Bence, Imre, Tímea, Iván, Kristóf, Szabó, Pál, Erdő, Franciska
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559210/
https://www.ncbi.nlm.nih.gov/pubmed/32854319
http://dx.doi.org/10.3390/pharmaceutics12090804
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author Bajza, Ágnes
Kocsis, Dorottya
Berezvai, Orsolya
Laki, András József
Lukács, Bence
Imre, Tímea
Iván, Kristóf
Szabó, Pál
Erdő, Franciska
author_facet Bajza, Ágnes
Kocsis, Dorottya
Berezvai, Orsolya
Laki, András József
Lukács, Bence
Imre, Tímea
Iván, Kristóf
Szabó, Pál
Erdő, Franciska
author_sort Bajza, Ágnes
collection PubMed
description The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery.
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spelling pubmed-75592102020-10-29 Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device Bajza, Ágnes Kocsis, Dorottya Berezvai, Orsolya Laki, András József Lukács, Bence Imre, Tímea Iván, Kristóf Szabó, Pál Erdő, Franciska Pharmaceutics Article The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery. MDPI 2020-08-25 /pmc/articles/PMC7559210/ /pubmed/32854319 http://dx.doi.org/10.3390/pharmaceutics12090804 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bajza, Ágnes
Kocsis, Dorottya
Berezvai, Orsolya
Laki, András József
Lukács, Bence
Imre, Tímea
Iván, Kristóf
Szabó, Pál
Erdő, Franciska
Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title_full Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title_fullStr Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title_full_unstemmed Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title_short Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device
title_sort verification of p-glycoprotein function at the dermal barrier in diffusion cells and dynamic “skin-on-a-chip” microfluidic device
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559210/
https://www.ncbi.nlm.nih.gov/pubmed/32854319
http://dx.doi.org/10.3390/pharmaceutics12090804
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