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Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy

Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce...

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Autores principales: Kaltschmidt, Bernhard P., Ennen, Inga, Greiner, Johannes F. W., Dietsch, Robin, Patel, Anant, Kaltschmidt, Barbara, Kaltschmidt, Christian, Hütten, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277086/
https://www.ncbi.nlm.nih.gov/pubmed/32369920
http://dx.doi.org/10.3390/biomedicines8050105
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author Kaltschmidt, Bernhard P.
Ennen, Inga
Greiner, Johannes F. W.
Dietsch, Robin
Patel, Anant
Kaltschmidt, Barbara
Kaltschmidt, Christian
Hütten, Andreas
author_facet Kaltschmidt, Bernhard P.
Ennen, Inga
Greiner, Johannes F. W.
Dietsch, Robin
Patel, Anant
Kaltschmidt, Barbara
Kaltschmidt, Christian
Hütten, Andreas
author_sort Kaltschmidt, Bernhard P.
collection PubMed
description Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating thymol, menthol, camphor and 1,8-cineol, characterize them via cryo transmission electron microscopy and assess their bactericidal properties. While control- and cineol-invasomes are similarly distributed between unilamellar and bilamellar vesicles, a shift towards unilamellar invasomes is observable after encapsulation of thymol, menthol or camphor. Thymol- and camphor-invasomes show a size reduction, whereas menthol-invasomes are enlarged and cineol-invasomes remain unchanged compared to control. While thymol-invasomes lead to the strongest growth inhibition of S. aureus, camphor- or cineol-invasomes mediate cell death and S. aureus growth is not affected by menthol-invasomes. Flow cytometric analysis validate that invasomes comprising thymol are highly bactericidal to S. aureus. Notably, treatment with thymol-invasomes does not affect survival of Gram-negative E. coli. In summary, we successfully produce terpenoid-invasomes and demonstrate that particularly thymol-invasomes show a strong selective activity against Gram-positive bacteria. Our findings provide a promising approach to increase the bioavailability of terpenoid-based drugs and may be directly applicable for treating severe bacterial infections such as methicillin-resistant S. aureus.
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spelling pubmed-72770862020-06-15 Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy Kaltschmidt, Bernhard P. Ennen, Inga Greiner, Johannes F. W. Dietsch, Robin Patel, Anant Kaltschmidt, Barbara Kaltschmidt, Christian Hütten, Andreas Biomedicines Article Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating thymol, menthol, camphor and 1,8-cineol, characterize them via cryo transmission electron microscopy and assess their bactericidal properties. While control- and cineol-invasomes are similarly distributed between unilamellar and bilamellar vesicles, a shift towards unilamellar invasomes is observable after encapsulation of thymol, menthol or camphor. Thymol- and camphor-invasomes show a size reduction, whereas menthol-invasomes are enlarged and cineol-invasomes remain unchanged compared to control. While thymol-invasomes lead to the strongest growth inhibition of S. aureus, camphor- or cineol-invasomes mediate cell death and S. aureus growth is not affected by menthol-invasomes. Flow cytometric analysis validate that invasomes comprising thymol are highly bactericidal to S. aureus. Notably, treatment with thymol-invasomes does not affect survival of Gram-negative E. coli. In summary, we successfully produce terpenoid-invasomes and demonstrate that particularly thymol-invasomes show a strong selective activity against Gram-positive bacteria. Our findings provide a promising approach to increase the bioavailability of terpenoid-based drugs and may be directly applicable for treating severe bacterial infections such as methicillin-resistant S. aureus. MDPI 2020-05-01 /pmc/articles/PMC7277086/ /pubmed/32369920 http://dx.doi.org/10.3390/biomedicines8050105 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
Kaltschmidt, Bernhard P.
Ennen, Inga
Greiner, Johannes F. W.
Dietsch, Robin
Patel, Anant
Kaltschmidt, Barbara
Kaltschmidt, Christian
Hütten, Andreas
Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title_full Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title_fullStr Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title_full_unstemmed Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title_short Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
title_sort preparation of terpenoid-invasomes with selective activity against s. aureus and characterization by cryo transmission electron microscopy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277086/
https://www.ncbi.nlm.nih.gov/pubmed/32369920
http://dx.doi.org/10.3390/biomedicines8050105
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