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Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes

The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this...

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Autores principales: Luengo, Javiana, Schneider, Marc, Schneider, Anna M., Lehr, Claus-Michael, Schaefer, Ulrich F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538358/
https://www.ncbi.nlm.nih.gov/pubmed/34683901
http://dx.doi.org/10.3390/pharmaceutics13101608
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author Luengo, Javiana
Schneider, Marc
Schneider, Anna M.
Lehr, Claus-Michael
Schaefer, Ulrich F.
author_facet Luengo, Javiana
Schneider, Marc
Schneider, Anna M.
Lehr, Claus-Michael
Schaefer, Ulrich F.
author_sort Luengo, Javiana
collection PubMed
description The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this aim, different vehicles under non-buffered and buffered conditions and different skin models (human heat separated epidermis and reconstructed human epidermis equivalents) were tested. Permeation experiments were performed using static Franz diffusion cells under infinite dosing conditions. Already the presence of drug-free nanoparticles increased drug permeation across the skin. Drug permeation was even enhanced when applying drug-loaded nanoparticles. In contrast, buffered vehicles with different pH values (pH 5.4–7.4) revealed the influence of the pH on the permeation of FFA. The change of the surrounding pH of the biodegradable nanoparticulate system was demonstrated and visualized using pH-sensitive fluorescent probes. While a potential contribution of hair follicles could be ruled out, our data suggest that the enhanced permeation of FFA through human skin in the presence of PLGA nanoparticles is mediated by a locally decreased pH during hydrolytic degradation of this polymer. This hypothesis is supported by the observation that skin permeation of the weak base caffeine was not affected.
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spelling pubmed-85383582021-10-24 Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes Luengo, Javiana Schneider, Marc Schneider, Anna M. Lehr, Claus-Michael Schaefer, Ulrich F. Pharmaceutics Article The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this aim, different vehicles under non-buffered and buffered conditions and different skin models (human heat separated epidermis and reconstructed human epidermis equivalents) were tested. Permeation experiments were performed using static Franz diffusion cells under infinite dosing conditions. Already the presence of drug-free nanoparticles increased drug permeation across the skin. Drug permeation was even enhanced when applying drug-loaded nanoparticles. In contrast, buffered vehicles with different pH values (pH 5.4–7.4) revealed the influence of the pH on the permeation of FFA. The change of the surrounding pH of the biodegradable nanoparticulate system was demonstrated and visualized using pH-sensitive fluorescent probes. While a potential contribution of hair follicles could be ruled out, our data suggest that the enhanced permeation of FFA through human skin in the presence of PLGA nanoparticles is mediated by a locally decreased pH during hydrolytic degradation of this polymer. This hypothesis is supported by the observation that skin permeation of the weak base caffeine was not affected. MDPI 2021-10-03 /pmc/articles/PMC8538358/ /pubmed/34683901 http://dx.doi.org/10.3390/pharmaceutics13101608 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luengo, Javiana
Schneider, Marc
Schneider, Anna M.
Lehr, Claus-Michael
Schaefer, Ulrich F.
Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title_full Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title_fullStr Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title_full_unstemmed Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title_short Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes
title_sort human skin permeation enhancement using plga nanoparticles is mediated by local ph changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538358/
https://www.ncbi.nlm.nih.gov/pubmed/34683901
http://dx.doi.org/10.3390/pharmaceutics13101608
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