Zn²⁺-Driven Tavaborole-Adenosine Hydrogel: A Strategy for Enhanced Solubility, Sustained Release, and Antifungal...

Onychomycosis is a common fungal nail infection, causing nail thickening and discoloration. Tavaborole, a topical antifungal, has fewer side effects but requires long treatment periods and often results in low cure rates. In this study, we developed a Zn²⁺-driven tavaborole-adenosine (AT-Zn²⁺) hydrogel to improve its therapeutic effect. The hydrogel enhanced tavaborole's solubility, drug loading, and antifungal activity. Characterization by nuclear magnetic resonance (NMR), ultraviolet-visible (UV-vis) spectroscopy, and transmission electron microscopy (TEM) confirmed its successful synthesis and nanofiber structure. In vitro release tests showed that about 65% of tavaborole was released in PBS at pH 5.5 over 24 h, indicating pH-sensitive drug release for targeted therapy. Permeation studies using a bovine hoof model showed effective tavaborole penetration through keratinized tissues with a steady-state flux of 162 μg/cm²/h. The AT-Zn²⁺ hydrogel demonstrated lower minimum inhibitory concentrations (MICs) for C. albicans (0.00156 mM) and A. fumigatus (0.025 mM) compared to those of tavaborole alone. In a bovine onychomycosis model, the hydrogel showed stronger antifungal effects than the tavaborole solution. Cytotoxicity assays on RAW 264.7 cells indicated good biocompatibility with >85% cell viability. These findings suggest that the AT-Zn²⁺ hydrogel holds significant potential as a clinically effective antifungal agent.