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Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy

Nanocrystals represent an improvement over the traditional nanocarriers for dermal application, providing the advantages of 100% drug loading, a large surface area, increased adhesion, and the potential for hair follicle targeting. To investigate their advantage for drug delivery, compared to a base...

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Autores principales: Lohan, Silke B., Saeidpour, Siavash, Colombo, Miriam, Staufenbiel, Sven, Unbehauen, Michael, Wolde-Kidan, Amanuel, Netz, Roland R., Bodmeier, Roland, Haag, Rainer, Teutloff, Christian, Bittl, Robert, Meinke, Martina C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284345/
https://www.ncbi.nlm.nih.gov/pubmed/32349460
http://dx.doi.org/10.3390/pharmaceutics12050400
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author Lohan, Silke B.
Saeidpour, Siavash
Colombo, Miriam
Staufenbiel, Sven
Unbehauen, Michael
Wolde-Kidan, Amanuel
Netz, Roland R.
Bodmeier, Roland
Haag, Rainer
Teutloff, Christian
Bittl, Robert
Meinke, Martina C.
author_facet Lohan, Silke B.
Saeidpour, Siavash
Colombo, Miriam
Staufenbiel, Sven
Unbehauen, Michael
Wolde-Kidan, Amanuel
Netz, Roland R.
Bodmeier, Roland
Haag, Rainer
Teutloff, Christian
Bittl, Robert
Meinke, Martina C.
author_sort Lohan, Silke B.
collection PubMed
description Nanocrystals represent an improvement over the traditional nanocarriers for dermal application, providing the advantages of 100% drug loading, a large surface area, increased adhesion, and the potential for hair follicle targeting. To investigate their advantage for drug delivery, compared to a base cream formulation, dexamethasone (Dx), a synthetic glucocorticoid frequently used for the treatment of inflammatory skin diseases, was covalently linked with the paramagnetic probe 3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) to DxPCA. To investigate the penetration efficiency between these two vehicles, electron paramagnetic resonance (EPR) spectroscopy was used, which allows the quantification of a spin-labeled drug in different skin layers and the monitoring of the drug release. The penetration behavior in excised healthy and barrier-disrupted porcine skin was monitored by EPR, and subsequently analyzed using a numerical diffusion model. As a result, diffusion constants and free energy values in the different layers of the skin were identified for both formulations. Dx-nanocrystals showed a significantly increased drug amount that penetrated into viable epidermis and dermis of intact (factor 3) and barrier-disrupted skin (factor 2.1) compared to the base cream formulation. Furthermore, the observed fast delivery of the spin-labeled drug into the skin (80% DxPCA within 30 min) and a successive release from the aggregate unit into the viable tissue makes these nanocrystals very attractive for clinical applications.
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spelling pubmed-72843452020-08-13 Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy Lohan, Silke B. Saeidpour, Siavash Colombo, Miriam Staufenbiel, Sven Unbehauen, Michael Wolde-Kidan, Amanuel Netz, Roland R. Bodmeier, Roland Haag, Rainer Teutloff, Christian Bittl, Robert Meinke, Martina C. Pharmaceutics Article Nanocrystals represent an improvement over the traditional nanocarriers for dermal application, providing the advantages of 100% drug loading, a large surface area, increased adhesion, and the potential for hair follicle targeting. To investigate their advantage for drug delivery, compared to a base cream formulation, dexamethasone (Dx), a synthetic glucocorticoid frequently used for the treatment of inflammatory skin diseases, was covalently linked with the paramagnetic probe 3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) to DxPCA. To investigate the penetration efficiency between these two vehicles, electron paramagnetic resonance (EPR) spectroscopy was used, which allows the quantification of a spin-labeled drug in different skin layers and the monitoring of the drug release. The penetration behavior in excised healthy and barrier-disrupted porcine skin was monitored by EPR, and subsequently analyzed using a numerical diffusion model. As a result, diffusion constants and free energy values in the different layers of the skin were identified for both formulations. Dx-nanocrystals showed a significantly increased drug amount that penetrated into viable epidermis and dermis of intact (factor 3) and barrier-disrupted skin (factor 2.1) compared to the base cream formulation. Furthermore, the observed fast delivery of the spin-labeled drug into the skin (80% DxPCA within 30 min) and a successive release from the aggregate unit into the viable tissue makes these nanocrystals very attractive for clinical applications. MDPI 2020-04-27 /pmc/articles/PMC7284345/ /pubmed/32349460 http://dx.doi.org/10.3390/pharmaceutics12050400 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
Lohan, Silke B.
Saeidpour, Siavash
Colombo, Miriam
Staufenbiel, Sven
Unbehauen, Michael
Wolde-Kidan, Amanuel
Netz, Roland R.
Bodmeier, Roland
Haag, Rainer
Teutloff, Christian
Bittl, Robert
Meinke, Martina C.
Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title_full Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title_fullStr Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title_full_unstemmed Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title_short Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
title_sort nanocrystals for improved drug delivery of dexamethasone in skin investigated by epr spectroscopy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284345/
https://www.ncbi.nlm.nih.gov/pubmed/32349460
http://dx.doi.org/10.3390/pharmaceutics12050400
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