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Purpose <p>Onychomycosis impacts almost 5% of the overall population in India, mainly in moist and elevated humid regions. Patients with diabetes are 2–3 times more likely to develop onychomycosis than healthy individuals. Available systemic therapies have several unavoidable drawbacks like hepatic side effect, drug-drug interaction, non-economical due to longer duration of treatment and the topical delivery systems faces a significant hurdle in drug permeation through the nail plate. A novel topical nanoemulgel formulation is prepared to surmount these inevitable drawbacks.</p> Methods <p>For transungal drug administration, nanoemulsions (NEs) using a pseudo-ternary phase diagram were developed. Next, by adding a 2% w/w gelling agent (Carbopol-934) to the external phase, nanoemulsions were transformed into nanoemulgels (NEGs). An in-vitro drug release study was conducted to optimize the best formulation. The optimized NEG formulation was integrated with permeation enhancers. After that, fabricated formulations underwent several physicochemical and molecular behavioral studies.</p> Results <p>The nanoemulsions’ droplet sizes varied from 47.62 to 192.10&#xa0;nm, while the zeta potential varied from − 0.6 to -6.1 mV. Among all the optimized formulations, NEG-1SS showed the highest in-vitro drug release of 98% in 9&#xa0;h, whereas the marketed formulation showed the lowest drug release of 43% in 13&#xa0;h. The NEG-1, NEG-1SS, and NEG-1SL displayed a noteworthy zone of inhibition against tested fungal strains, which was almost double that of the zone of inhibition shown by the market formulation. Ex-vivo drug uptake investigations through clipped nails demonstrated an intake of 108.42 to 119.04&#xa0;µg/mm<sup>2</sup>. In a molecular docking study, Ketoconazole scored favorably against the targeted enzyme lanosterol 14-alpha-demethylase.</p> Discussion and Conclusion <p>The observed results suggested that the optimized formulations showed better in-vitro drug release and in-vitro antifungal activity against the tested fungal strains than the marketed formulation (Ketostar). Optimized formulation NEG-1SS showed better ex-vivo drug uptake among all the optimized nanoemulgels, suggesting potential activity of sodium sulfide as a transungual permeation enhancer. This enhanced drug permeation will enhance the presence of drug in the nail bed, which will improve the antifungal activity of drug in the targeted site. The results showed that the NEG-1SS can potentially transform topical antifungal therapies by surmounting significant hurdles like binding and permeation of drug through the nail plate. This formulation may offer a viable alternative to systemic antifungals, reducing adverse effects and improving patient compliance by increasing the drug permeation into the desired area.</p>

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Design and Development of Ketoconazole Loaded Nanoemulgel for the Improved Topical Therapy of Onychomycosis Using Chemical Penetration Enhancers

  • 期刊论文

  • 发表日期：

    2025年5月31日

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  • Yashwant Giri,
  • Amulyaratna Behera,
  • Biswaranjan Mohanty,
  • Sk Habibullah,
  • Pradyumna Kumar Dixit,
  • Gurudutta Pattnaik,
  • B. Jyotirmayee

摘要

Purpose

Onychomycosis impacts almost 5% of the overall population in India, mainly in moist and elevated humid regions. Patients with diabetes are 2–3 times more likely to develop onychomycosis than healthy individuals. Available systemic therapies have several unavoidable drawbacks like hepatic side effect, drug-drug interaction, non-economical due to longer duration of treatment and the topical delivery systems faces a significant hurdle in drug permeation through the nail plate. A novel topical nanoemulgel formulation is prepared to surmount these inevitable drawbacks.

Methods

For transungal drug administration, nanoemulsions (NEs) using a pseudo-ternary phase diagram were developed. Next, by adding a 2% w/w gelling agent (Carbopol-934) to the external phase, nanoemulsions were transformed into nanoemulgels (NEGs). An in-vitro drug release study was conducted to optimize the best formulation. The optimized NEG formulation was integrated with permeation enhancers. After that, fabricated formulations underwent several physicochemical and molecular behavioral studies.

Results

The nanoemulsions’ droplet sizes varied from 47.62 to 192.10 nm, while the zeta potential varied from − 0.6 to -6.1 mV. Among all the optimized formulations, NEG-1SS showed the highest in-vitro drug release of 98% in 9 h, whereas the marketed formulation showed the lowest drug release of 43% in 13 h. The NEG-1, NEG-1SS, and NEG-1SL displayed a noteworthy zone of inhibition against tested fungal strains, which was almost double that of the zone of inhibition shown by the market formulation. Ex-vivo drug uptake investigations through clipped nails demonstrated an intake of 108.42 to 119.04 µg/mm2. In a molecular docking study, Ketoconazole scored favorably against the targeted enzyme lanosterol 14-alpha-demethylase.

Discussion and Conclusion

The observed results suggested that the optimized formulations showed better in-vitro drug release and in-vitro antifungal activity against the tested fungal strains than the marketed formulation (Ketostar). Optimized formulation NEG-1SS showed better ex-vivo drug uptake among all the optimized nanoemulgels, suggesting potential activity of sodium sulfide as a transungual permeation enhancer. This enhanced drug permeation will enhance the presence of drug in the nail bed, which will improve the antifungal activity of drug in the targeted site. The results showed that the NEG-1SS can potentially transform topical antifungal therapies by surmounting significant hurdles like binding and permeation of drug through the nail plate. This formulation may offer a viable alternative to systemic antifungals, reducing adverse effects and improving patient compliance by increasing the drug permeation into the desired area.