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Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) coul...

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Autores principales: Otto, Matthias, Krebs, Jörg, Welker, Peter, Holm, René, Thiel, Manfred, Gattinoni, Luciano, Quintel, Michael, Tsagogiorgas, Charalambos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004724/
https://www.ncbi.nlm.nih.gov/pubmed/33806903
http://dx.doi.org/10.3390/pharmaceutics13030431
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author Otto, Matthias
Krebs, Jörg
Welker, Peter
Holm, René
Thiel, Manfred
Gattinoni, Luciano
Quintel, Michael
Tsagogiorgas, Charalambos
author_facet Otto, Matthias
Krebs, Jörg
Welker, Peter
Holm, René
Thiel, Manfred
Gattinoni, Luciano
Quintel, Michael
Tsagogiorgas, Charalambos
author_sort Otto, Matthias
collection PubMed
description Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.
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spelling pubmed-80047242021-03-29 Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome Otto, Matthias Krebs, Jörg Welker, Peter Holm, René Thiel, Manfred Gattinoni, Luciano Quintel, Michael Tsagogiorgas, Charalambos Pharmaceutics Article Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics. MDPI 2021-03-23 /pmc/articles/PMC8004724/ /pubmed/33806903 http://dx.doi.org/10.3390/pharmaceutics13030431 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Otto, Matthias
Krebs, Jörg
Welker, Peter
Holm, René
Thiel, Manfred
Gattinoni, Luciano
Quintel, Michael
Tsagogiorgas, Charalambos
Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title_full Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title_fullStr Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title_full_unstemmed Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title_short Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
title_sort inhalationally administered semifluorinated alkanes (sfas) as drug carriers in an experimental model of acute respiratory distress syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004724/
https://www.ncbi.nlm.nih.gov/pubmed/33806903
http://dx.doi.org/10.3390/pharmaceutics13030431
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