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February 9, 20260 citations

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

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YSYehua SunHSHaowei ShaCLChangyang Lei

Key Points

  • To develop a Zn2+-driven tavaborole-adenosine hydrogel to enhance the solubility, sustained release, and antifungal efficacy of tavaborole.
  • Developed a Zn2+-driven hydrogel for tavaborole and adenosine.
  • Characterized the hydrogel using NMR, UV-vis spectroscopy, and TEM.
  • Conducted in vitro release tests at pH 5.5.
  • Performed permeation studies using a bovine hoof model.
  • Assessed cytotoxicity on RAW 264.7 cells.
  • Hydrogel released about 65% of tavaborole within 24 hours at pH 5.5.
  • Significantly improved penetration of tavaborole into keratinized tissues with a steady-state flux of 162 µg/cm²/h.
  • Demonstrated lower MICs for C. albicans (0.00156 mM) and A. fumigatus (0.025 mM) compared to tavaborole alone.
  • Showed stronger antifungal effects in a bovine onychomycosis model than tavaborole solutions.
  • Indicated over 85% cell viability, confirming good biocompatibility.

Abstract

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.

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Cite This Study

Sun et al. (2026) studied this question.

synapsesocial.com/papers/69897a35f0ec2af6756e891ahttps://doi.org/10.1021/acs.molpharmaceut.5c01541
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