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In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis

The purpose of our research was the development of Amphotericin B-loaded in situ gelling nanofibers for the treatment of keratomycosis. Different formulation strategies were applied to increase the drug load of the sparingly water-soluble Amphotericin B in electrospun Gellan Gum/Pullulan fibers. The...

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Autores principales: Göttel, Benedikt, Lucas, Henrike, Syrowatka, Frank, Knolle, Wolfgang, Kuntsche, Judith, Heinzelmann, Joana, Viestenz, Arne, Mäder, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786432/
https://www.ncbi.nlm.nih.gov/pubmed/33425866
http://dx.doi.org/10.3389/fbioe.2020.600384
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author Göttel, Benedikt
Lucas, Henrike
Syrowatka, Frank
Knolle, Wolfgang
Kuntsche, Judith
Heinzelmann, Joana
Viestenz, Arne
Mäder, Karsten
author_facet Göttel, Benedikt
Lucas, Henrike
Syrowatka, Frank
Knolle, Wolfgang
Kuntsche, Judith
Heinzelmann, Joana
Viestenz, Arne
Mäder, Karsten
author_sort Göttel, Benedikt
collection PubMed
description The purpose of our research was the development of Amphotericin B-loaded in situ gelling nanofibers for the treatment of keratomycosis. Different formulation strategies were applied to increase the drug load of the sparingly water-soluble Amphotericin B in electrospun Gellan Gum/Pullulan fibers. These include bile salt addition, encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and formation of a polymeric Amphotericin B polyelectrolyte complex. The Amphotericin B polyelectrolyte complex (AmpB-Eu L) performed best and was very effective against the fungal strain Issatchenkia orientalis in vitro. The complex was characterized in detail by attenuated total reflection infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. A heat induced stress test was carried out to ensure the stability of the polyelectrolyte complex. To gain information about the cellular tolerance of the developed polyelectrolyte complex a new, innovative multilayered-stratified human cornea cell model was used for determination of the cellular toxicity in vitro. For a safe therapy, the applied ophthalmic drug delivery system has to be sterile. Sterilization by electron irradiation caused not degradation of pure Amphotericin B and also for the bile salt complex. Furthermore, the developed Amphotericin B polyelectrolyte complex was not degraded by the irradiation process. In conclusion, a new polyelectrolyte Amphotericin B complex has been found which retains the antifungal activity of the drug with sufficient stability against irradiation-sterilization induced drug degradation. Furthermore, in comparison with the conventional used eye drop formulation, the new AmpB-complex loaded nanofibers were less toxic to cornea cells in vitro. Electrospinning of the Amphotericin B polyelectrolyte complex with Gellan Gum/ Pullulan leads to the formation of nanofibers with in situ gelling properties, which is a new and promising option for the treatment of keratomycosis.
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spelling pubmed-77864322021-01-07 In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis Göttel, Benedikt Lucas, Henrike Syrowatka, Frank Knolle, Wolfgang Kuntsche, Judith Heinzelmann, Joana Viestenz, Arne Mäder, Karsten Front Bioeng Biotechnol Bioengineering and Biotechnology The purpose of our research was the development of Amphotericin B-loaded in situ gelling nanofibers for the treatment of keratomycosis. Different formulation strategies were applied to increase the drug load of the sparingly water-soluble Amphotericin B in electrospun Gellan Gum/Pullulan fibers. These include bile salt addition, encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and formation of a polymeric Amphotericin B polyelectrolyte complex. The Amphotericin B polyelectrolyte complex (AmpB-Eu L) performed best and was very effective against the fungal strain Issatchenkia orientalis in vitro. The complex was characterized in detail by attenuated total reflection infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. A heat induced stress test was carried out to ensure the stability of the polyelectrolyte complex. To gain information about the cellular tolerance of the developed polyelectrolyte complex a new, innovative multilayered-stratified human cornea cell model was used for determination of the cellular toxicity in vitro. For a safe therapy, the applied ophthalmic drug delivery system has to be sterile. Sterilization by electron irradiation caused not degradation of pure Amphotericin B and also for the bile salt complex. Furthermore, the developed Amphotericin B polyelectrolyte complex was not degraded by the irradiation process. In conclusion, a new polyelectrolyte Amphotericin B complex has been found which retains the antifungal activity of the drug with sufficient stability against irradiation-sterilization induced drug degradation. Furthermore, in comparison with the conventional used eye drop formulation, the new AmpB-complex loaded nanofibers were less toxic to cornea cells in vitro. Electrospinning of the Amphotericin B polyelectrolyte complex with Gellan Gum/ Pullulan leads to the formation of nanofibers with in situ gelling properties, which is a new and promising option for the treatment of keratomycosis. Frontiers Media S.A. 2020-12-21 /pmc/articles/PMC7786432/ /pubmed/33425866 http://dx.doi.org/10.3389/fbioe.2020.600384 Text en Copyright © 2020 Göttel, Lucas, Syrowatka, Knolle, Kuntsche, Heinzelmann, Viestenz and Mäder. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Göttel, Benedikt
Lucas, Henrike
Syrowatka, Frank
Knolle, Wolfgang
Kuntsche, Judith
Heinzelmann, Joana
Viestenz, Arne
Mäder, Karsten
In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title_full In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title_fullStr In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title_full_unstemmed In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title_short In situ Gelling Amphotericin B Nanofibers: A New Option for the Treatment of Keratomycosis
title_sort in situ gelling amphotericin b nanofibers: a new option for the treatment of keratomycosis
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786432/
https://www.ncbi.nlm.nih.gov/pubmed/33425866
http://dx.doi.org/10.3389/fbioe.2020.600384
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