Harnessing Cu- and Fe-based metal-organic frameworks as innovative nanocarriers for enhanced fluconazole delivery in topical management of Candida albicans

Fungal infections pose significant challenges in healthcare, with current treatments often limited by low efficacy and side effects. This study explores fluconazole (FLCZ) loaded metal-organic frameworks (MOF) as innovative nanocarriers to enhance antifungal therapy through synergistic action and controlled drug release. MOF synthesized using copper (Cu) and iron (Fe) metals with suitable linker via the room temperature conversion method were converted into topical gels using Carbopol® 971 NP. Comprehensive evaluations revealed that the Cu- and Fe-based MOF gels were clear and translucent, with skin-compatible pH (5.96 ± 0.07 and 5.02 ± 0.04, respectively), high drug content (>98 %w/w), and favorable application properties, including pseudoplastic flow, good spreadability (35 ± 2 mm and 23 ± 3 mm), and high viscosity (6489.33 ± 7.15 cps and 6247.41 ± 5.69 cps, respectively). Drug release studies showed sustained profiles with Cu- and Fe-MOF gels following a Higuchi matrix diffusion-controlled mechanism. In-vitro antifungal studies demonstrated enhanced efficacy, with larger zones of inhibition against Candida albicans compared to marketed formulation, indicating a synergistic mechanism of action. Acute dermal toxicity assessment confirmed the safety of MOF gels, with minimal skin irritation and improved histological outcomes. This investigation highlights the potential of MOF-based gels as advanced nanocarrier systems for fungal infections, offering controlled release, enhanced antifungal activity, and reduced skin toxicity, paving the way for effective, targeted antifungal therapies.