Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
<b>Background/Objectives</b>: Filamentous fungi, in particular the species <i>Aspergillus</i>, <i>Scedosporium</i>, and <i>Exophiala</i>, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity...
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2025-05-01
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| Online Access: | https://www.mdpi.com/1999-4923/17/6/725 |
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| author | Shaul D. Cemal María F. Ladetto Katherine Hermida Alava Gila Kazimirsky Marcela Cucher Romina J. Glisoni María L. Cuestas Gerardo Byk |
| author_facet | Shaul D. Cemal María F. Ladetto Katherine Hermida Alava Gila Kazimirsky Marcela Cucher Romina J. Glisoni María L. Cuestas Gerardo Byk |
| author_sort | Shaul D. Cemal |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Filamentous fungi, in particular the species <i>Aspergillus</i>, <i>Scedosporium</i>, and <i>Exophiala</i>, 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. <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions</b>: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs. |
| format | Article |
| id | doaj-art-09ba27a0a97e4db482f016cdbcc2935a |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-09ba27a0a97e4db482f016cdbcc2935a2025-08-20T02:21:52ZengMDPI AGPharmaceutics1999-49232025-05-0117672510.3390/pharmaceutics17060725Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis PatientsShaul D. Cemal0María F. Ladetto1Katherine Hermida Alava2Gila Kazimirsky3Marcela Cucher4Romina J. Glisoni5María L. Cuestas6Gerardo Byk7Department of Chemistry, Bar-Ilan University, Ramat Gan 5290002, IsraelInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), CONICET, Universidad de Buenos Aires, Buenos Aires 1121, ArgentinaInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), CONICET, Universidad de Buenos Aires, Buenos Aires 1121, ArgentinaDepartment of Chemistry, Bar-Ilan University, Ramat Gan 5290002, IsraelInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), CONICET, Universidad de Buenos Aires, Buenos Aires 1121, ArgentinaInstituto de Nanobiotecnología (NANOBIOTEC), CONICET, Universidad de Buenos Aires, Buenos Aires 1121, ArgentinaInstituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), CONICET, Universidad de Buenos Aires, Buenos Aires 1121, ArgentinaDepartment of Chemistry, Bar-Ilan University, Ramat Gan 5290002, Israel<b>Background/Objectives</b>: Filamentous fungi, in particular the species <i>Aspergillus</i>, <i>Scedosporium</i>, and <i>Exophiala</i>, 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. <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions</b>: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.https://www.mdpi.com/1999-4923/17/6/725voriconazolebiodegradable nanohydrogelscystic fibrosisCF mucus modeldrug deliverydrug release |
| spellingShingle | Shaul D. Cemal María F. Ladetto Katherine Hermida Alava Gila Kazimirsky Marcela Cucher Romina J. Glisoni María L. Cuestas Gerardo Byk Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients Pharmaceutics voriconazole biodegradable nanohydrogels cystic fibrosis CF mucus model drug delivery drug release |
| title | 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_short | Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients |
| title_sort | voriconazole loaded nanohydrogels towards optimized antifungal therapy for cystic fibrosis patients |
| topic | voriconazole biodegradable nanohydrogels cystic fibrosis CF mucus model drug delivery drug release |
| url | https://www.mdpi.com/1999-4923/17/6/725 |
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