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Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms
Purpose: Chronic infections of Candida albicans are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and Candida biofilms are associated with ocular fungal infections. The objective was to test the activity of na...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781556/ https://www.ncbi.nlm.nih.gov/pubmed/35056021 http://dx.doi.org/10.3390/pathogens11010073 |
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author | Alakkad, Abdulghani Stapleton, Paul Schlosser, Corinna Murdan, Sudaxshina Odunze, Uchechukwu Schatzlein, Andreas Uchegbu, Ijeoma F. |
author_facet | Alakkad, Abdulghani Stapleton, Paul Schlosser, Corinna Murdan, Sudaxshina Odunze, Uchechukwu Schatzlein, Andreas Uchegbu, Ijeoma F. |
author_sort | Alakkad, Abdulghani |
collection | PubMed |
description | Purpose: Chronic infections of Candida albicans are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and Candida biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against Candida biofilms. Methods: AmB was encapsulated in the Molecular Envelope Technology (MET, N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) nanoparticles and tested against Candida biofilms in vitro. Confocal laser scanning microscopy (CLSM) imaging of MET nanoparticles’ penetration into experimental biofilms was carried out and a MET-AmB eye drop formulation was tested for its stability. Results: MET-AmB formulations demonstrated superior activity towards C. albicans biofilms in vitro with the EC50 being ~30 times lower than AmB alone (EC50 MET-AmB = 1.176 μg mL(−1), EC50 AmB alone = 29.09 μg mL(−1)). A similar superior activity was found for Candida glabrata biofilms, where the EC50 was ~10× lower than AmB alone (EC50 MET-AmB = 0.0253 μg mL(−1), EC50 AmB alone = 0.289 μg mL(−1)). CLSM imaging revealed that MET nanoparticles penetrated through the C. albicans biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against C. albicans cells in suspension (MET-AmB MIC90 = 0.125 μg mL(−1), AmB alone MIC90 = 0.250 μg mL(−1)). MET-AmB eye drops were stable at room temperature for at least 28 days. Conclusions: These biofilm activity findings raise the possibility that MET-loaded nanoparticles may be used to tackle Candida biofilm infections, such as refractory ocular fungal infections. |
format | Online Article Text |
id | pubmed-8781556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87815562022-01-22 Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms Alakkad, Abdulghani Stapleton, Paul Schlosser, Corinna Murdan, Sudaxshina Odunze, Uchechukwu Schatzlein, Andreas Uchegbu, Ijeoma F. Pathogens Article Purpose: Chronic infections of Candida albicans are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and Candida biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against Candida biofilms. Methods: AmB was encapsulated in the Molecular Envelope Technology (MET, N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) nanoparticles and tested against Candida biofilms in vitro. Confocal laser scanning microscopy (CLSM) imaging of MET nanoparticles’ penetration into experimental biofilms was carried out and a MET-AmB eye drop formulation was tested for its stability. Results: MET-AmB formulations demonstrated superior activity towards C. albicans biofilms in vitro with the EC50 being ~30 times lower than AmB alone (EC50 MET-AmB = 1.176 μg mL(−1), EC50 AmB alone = 29.09 μg mL(−1)). A similar superior activity was found for Candida glabrata biofilms, where the EC50 was ~10× lower than AmB alone (EC50 MET-AmB = 0.0253 μg mL(−1), EC50 AmB alone = 0.289 μg mL(−1)). CLSM imaging revealed that MET nanoparticles penetrated through the C. albicans biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against C. albicans cells in suspension (MET-AmB MIC90 = 0.125 μg mL(−1), AmB alone MIC90 = 0.250 μg mL(−1)). MET-AmB eye drops were stable at room temperature for at least 28 days. Conclusions: These biofilm activity findings raise the possibility that MET-loaded nanoparticles may be used to tackle Candida biofilm infections, such as refractory ocular fungal infections. MDPI 2022-01-07 /pmc/articles/PMC8781556/ /pubmed/35056021 http://dx.doi.org/10.3390/pathogens11010073 Text en © 2022 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 Alakkad, Abdulghani Stapleton, Paul Schlosser, Corinna Murdan, Sudaxshina Odunze, Uchechukwu Schatzlein, Andreas Uchegbu, Ijeoma F. Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title | Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title_full | Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title_fullStr | Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title_full_unstemmed | Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title_short | Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms |
title_sort | amphotericin b polymer nanoparticles show efficacy against candida species biofilms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781556/ https://www.ncbi.nlm.nih.gov/pubmed/35056021 http://dx.doi.org/10.3390/pathogens11010073 |
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