Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients

Autores
Cemal, Shaul D.; Ladetto, María Florencia; Hermida Alava, Katherine; Kazimirsky, Gila; Cucher, Marcela; Glisoni, Romina J.; Cuestas, María L.; Byk, Gerardo
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.
Centro de Investigación y Desarrollo en Fermentaciones Industriales
Materia
Química
voriconazole
biodegradable nanohydrogels
cystic fibrosis
CF mucus model
drug delivery
drug release
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/181882
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/181882
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis PatientsCemal, Shaul D.Ladetto, María FlorenciaHermida Alava, KatherineKazimirsky, GilaCucher, MarcelaGlisoni, Romina J.Cuestas, María L.Byk, GerardoQuímicavoriconazolebiodegradable nanohydrogelscystic fibrosisCF mucus modeldrug deliverydrug releaseBackground/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.Centro de Investigación y Desarrollo en Fermentaciones Industriales2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/181882enginfo:eu-repo/semantics/altIdentifier/issn/1999-4923info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17060725info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:30:31Zoai:sedici.unlp.edu.ar:10915/181882Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:30:32.07SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
title Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
spellingShingle Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
Cemal, Shaul D.
Química
voriconazole
biodegradable nanohydrogels
cystic fibrosis
CF mucus model
drug delivery
drug release
title_short Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
title_full Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
title_fullStr Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
title_full_unstemmed Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
title_sort Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
dc.creator.none.fl_str_mv Cemal, Shaul D.
Ladetto, María Florencia
Hermida Alava, Katherine
Kazimirsky, Gila
Cucher, Marcela
Glisoni, Romina J.
Cuestas, María L.
Byk, Gerardo
author Cemal, Shaul D.
author_facet Cemal, Shaul D.
Ladetto, María Florencia
Hermida Alava, Katherine
Kazimirsky, Gila
Cucher, Marcela
Glisoni, Romina J.
Cuestas, María L.
Byk, Gerardo
author_role author
author2 Ladetto, María Florencia
Hermida Alava, Katherine
Kazimirsky, Gila
Cucher, Marcela
Glisoni, Romina J.
Cuestas, María L.
Byk, Gerardo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Química
voriconazole
biodegradable nanohydrogels
cystic fibrosis
CF mucus model
drug delivery
drug release
topic Química
voriconazole
biodegradable nanohydrogels
cystic fibrosis
CF mucus model
drug delivery
drug release
dc.description.none.fl_txt_mv Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.
Centro de Investigación y Desarrollo en Fermentaciones Industriales
description Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.
publishDate 2025
dc.date.none.fl_str_mv 2025-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/181882
url http://sedici.unlp.edu.ar/handle/10915/181882
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1999-4923
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17060725
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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