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<p>Fungal skin infections present a considerable therapeutic challenge globally, underscoring the need for advanced drug delivery systems and novel antifungal agents to overcome issues of resistance, poor skin penetration, and recurrence. Itraconazole (ITZ) is a broad-spectrum triazole antifungal agent used in the treatment of dermatophytosis. ITZ is known for its poor and variable systemic bioavailability. This study aimed to formulate ITZ-loaded lipid-polymer hybrid nanoparticles (LPHNs) using a single-step emulsion solvent evaporation method. Optimized LPHNs were loaded in 1% w/v Carbopol gel and evaluated for spreadability, ex-vivo skin permeation and deposition, skin irritation study, and in-vitro antifungal activity against <i>Candida albicans</i>. Skin irritation, ex-vivo skin permeation and deposition, skin sensitization, and in-vivo antifungal studies were carried out in adult male Albino Wistar rats. Optimized spherical LPHNs displayed a particle size of 184.4&#xa0;nm, a polydispersity Index (PDI) of 0.191, and a zeta potential of -36.9 mV. Polymer and lipid had a positive effect on particle size. For optimized LPHN synthesis, 30&#xa0;mg of lipid and 20&#xa0;mg of polymer were recommended. LPHNs exhibited a biphasic release profile with an initial burst followed by sustained release, achieving 87.30 ± 3.01% release over 12&#xa0;h. The ITZ LPHNs-loaded gel demonstrated an acceptable pH, suitable viscosity, good spreadability, increased skin deposition, and no irritation, which indicates that it is appropriate for effective topical application. Dermal and epidermal layers of skin treated with formulations were intact with normal physiology. Statistical analysis revealed significantly lower skin permeation (<i>p</i> &lt; 0.01) and higher drug retention (<i>p</i> &lt; 0.001) for the LPHNs-loaded gel compared to the plain drug and marketed formulation. The formulation showed superior antifungal efficacy, with a significantly larger inhibition zone (<i>p</i> &lt; 0.05) and reduced <i>C. albicans</i> load (<i>p</i> &lt; 0.01) in vivo. These results confirm that the optimized LPHNs gel enhances localized drug retention and therapeutic effectiveness while minimizing systemic exposure and irritation.</p> Graphical Abstract <p></p>

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Lipid-Polymer Hybrid Nanoparticles Loaded Hydrogel Formulation for Enhanced Topical Delivery of Itraconazole: in Vitro and in Vivo Studies

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Namrata Deshmukh,
  • Rajendra Awasthi,
  • Dyandevi Mathure,
  • Vividha Dhapte-Pawar,
  • Atmaram Pawar

摘要

Fungal skin infections present a considerable therapeutic challenge globally, underscoring the need for advanced drug delivery systems and novel antifungal agents to overcome issues of resistance, poor skin penetration, and recurrence. Itraconazole (ITZ) is a broad-spectrum triazole antifungal agent used in the treatment of dermatophytosis. ITZ is known for its poor and variable systemic bioavailability. This study aimed to formulate ITZ-loaded lipid-polymer hybrid nanoparticles (LPHNs) using a single-step emulsion solvent evaporation method. Optimized LPHNs were loaded in 1% w/v Carbopol gel and evaluated for spreadability, ex-vivo skin permeation and deposition, skin irritation study, and in-vitro antifungal activity against Candida albicans. Skin irritation, ex-vivo skin permeation and deposition, skin sensitization, and in-vivo antifungal studies were carried out in adult male Albino Wistar rats. Optimized spherical LPHNs displayed a particle size of 184.4 nm, a polydispersity Index (PDI) of 0.191, and a zeta potential of -36.9 mV. Polymer and lipid had a positive effect on particle size. For optimized LPHN synthesis, 30 mg of lipid and 20 mg of polymer were recommended. LPHNs exhibited a biphasic release profile with an initial burst followed by sustained release, achieving 87.30 ± 3.01% release over 12 h. The ITZ LPHNs-loaded gel demonstrated an acceptable pH, suitable viscosity, good spreadability, increased skin deposition, and no irritation, which indicates that it is appropriate for effective topical application. Dermal and epidermal layers of skin treated with formulations were intact with normal physiology. Statistical analysis revealed significantly lower skin permeation (p < 0.01) and higher drug retention (p < 0.001) for the LPHNs-loaded gel compared to the plain drug and marketed formulation. The formulation showed superior antifungal efficacy, with a significantly larger inhibition zone (p < 0.05) and reduced C. albicans load (p < 0.01) in vivo. These results confirm that the optimized LPHNs gel enhances localized drug retention and therapeutic effectiveness while minimizing systemic exposure and irritation.

Graphical Abstract