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

Shaul D Cemal1, María F Ladetto2,3, Katherine Hermida Alava2

  • 1Department of Chemistry, Bar-Ilan University, Ramat Gan 5290002, Israel.

Pharmaceutics
|June 27, 2025
PubMed

Insights

Biodegradable nanohydrogels effectively deliver voriconazole (VRC) to combat fungal infections in cystic fibrosis (CF) lungs. This VRC nano-formulation overcomes mucus barriers, enhancing treatment efficacy against common CF lung fungi.

Area of Science:

  • Nanotechnology
  • Pharmaceutical Sciences
  • Infectious Diseases

Background:

  • Fungal lung infections by Aspergillus, Scedosporium, and Exophiala are common in cystic fibrosis (CF) patients.
  • Chronic colonization leads to lung function decline, with azole antifungals like voriconazole (VRC) showing limited efficacy due to mucus barriers.
  • Developing effective drug delivery systems is crucial for treating CF lung fungal infections.

Purpose of the Study:

  • To evaluate biodegradable nanohydrogels (NHGs) as nanocarriers for voriconazole (VRC) delivery in CF lungs.
  • To assess the physicochemical properties and pulmonary delivery potential of VRC-loaded NHGs.
  • To determine the enhanced antifungal efficacy of VRC-loaded NHGs against CF-associated fungi.

Main Methods:

  • Biodegradable NHGs were formulated to encapsulate VRC, with entrapment capacity up to 30 μg/mg.
  • Physicochemical properties, including size (100-400 nm) and colloidal stability in interstitial fluid, were analyzed.
  • In vitro cytocompatibility, drug release kinetics, and antifungal activity against CF sputum-derived fungi were evaluated.

Main Results:

  • VRC-loaded NHGs demonstrated excellent colloidal stability and high in vitro cytocompatibility.
  • The nano-formulation showed effective VRC release under tested conditions.
  • Antifungal activity of VRC-loaded NHGs was up to eight-fold greater than VRC suspension against CF fungi, even with artificial mucus.

Conclusions:

  • Biodegradable NHGs are a promising platform for formulating VRC for pulmonary delivery in CF patients.
  • VRC-loaded NHGs effectively overcome mucus barriers, enhancing antifungal potency.
  • These findings support the development of advanced nano-formulations for treating fungal lung infections in CF.
Keywords:
CF mucus modelbiodegradable nanohydrogelscystic fibrosisdrug deliverydrug releasevoriconazole

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