Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release

Area of Science:

• Biomaterials Science
• Mycology
• Drug Delivery

Background:

• Fungal infections, particularly those caused by Candida spp., pose significant health risks.
• Current antifungal treatments face challenges including toxicity and the emergence of antifungal resistance.
• Virulent Candida albicans secrete aspartic proteases (Saps) that facilitate tissue invasion.

Purpose of the Study:

• To develop novel fungi-responsive hydrogels for triggered antifungal drug delivery.
• To investigate the degradation of hydrogels in response to fungal enzymes.
• To evaluate the efficacy and safety of the developed drug delivery system.

Main Methods:

• Hydrogel backbone functionalized with Sap-cleavable peptide sequences.
• Encapsulation of liposomal antifungals within the hydrogel matrix.
• Assessment of hydrogel degradation kinetics in the presence of Saps.
• Evaluation of antifungal release profiles and in vitro efficacy against Candida albicans.
• Cytotoxicity assays using murine fibroblast and red blood cells.

Main Results:

• Hydrogels demonstrated effective degradation in the presence of Saps from Candida albicans.
• Liposomal antifungal release kinetics correlated with hydrogel degradation.
• Antifungal-loaded hydrogels successfully eradicated Candida albicans cultures in vitro.
• The hydrogel system remained stable in sterile murine wound fluid.
• Degradation products showed no significant cytotoxicity to mammalian cells.

Conclusions:

• Fungi-responsive hydrogels offer a promising platform for localized, on-demand antifungal drug delivery.
• This system can enhance treatment efficacy for fungal infections.
• The approach has the potential to reduce systemic exposure to antifungal drugs and combat resistance.