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<p>Ketoconazole (KTZ) is recognized for its broad-spectrum antifungal efficacy; however, its systemic administration is accompanied by notable adverse effects. Localized drug delivery can be a sophisticated solution to mitigate the KTZ-associated side effects. The current study aimed to design an innovative localized delivery system, based on KTZ-loaded polymeric nanoparticles in the configuration of a film-forming spray (FFS). The ionic gelation method was employed to craft polymeric nanoparticles of KTZ. KTZ-PNPs were precisely optimized using Design Expert® software and characterized for surface morphology and component compatibility through scanning electron microscopy (SEM) and Fourier transform infrared (FTIR), respectively. Optimized formulation exhibited a particle size of 233&#xa0;nm ± 2.0, a zeta potential of 35.6 ± 1.3&#xa0;mV, entrapment efficiency of 87% ± 0.02, and spherical morphology with particles ranging in nanoscale. Confirmation of KTZ deposition within skin layers was substantiated through ex vivo permeability and skin retentivity tests. The ultimate formulation demonstrated noteworthy antifungal activity against <i>Aspergillus flavus</i> and <i>Aspergillus niger</i>. Additionally, the non-irritating nature of the film-forming spray (FFS) was affirmed through a histological study conducted on rat skin. Consequently, the KTZ-PNPs-based FFS emerges as a promising candidate for the treatment of topical fungal infections.</p> Graphical Abstract <p></p>

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Ketoconazole Nanoparticles Based Film-Forming Spray-A Promising Breakthrough for Targeted Therapy

  • 期刊论文

  • 发表日期：

    2025年5月21日

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  • Wajhia Mumtaz,
  • Asim.ur. Rehman,
  • Parsa Gul,
  • Kifayat Ullah Shah,
  • Hashaam Akhtar,
  • Naveed Ahmed

摘要

Ketoconazole (KTZ) is recognized for its broad-spectrum antifungal efficacy; however, its systemic administration is accompanied by notable adverse effects. Localized drug delivery can be a sophisticated solution to mitigate the KTZ-associated side effects. The current study aimed to design an innovative localized delivery system, based on KTZ-loaded polymeric nanoparticles in the configuration of a film-forming spray (FFS). The ionic gelation method was employed to craft polymeric nanoparticles of KTZ. KTZ-PNPs were precisely optimized using Design Expert® software and characterized for surface morphology and component compatibility through scanning electron microscopy (SEM) and Fourier transform infrared (FTIR), respectively. Optimized formulation exhibited a particle size of 233 nm ± 2.0, a zeta potential of 35.6 ± 1.3 mV, entrapment efficiency of 87% ± 0.02, and spherical morphology with particles ranging in nanoscale. Confirmation of KTZ deposition within skin layers was substantiated through ex vivo permeability and skin retentivity tests. The ultimate formulation demonstrated noteworthy antifungal activity against Aspergillus flavus and Aspergillus niger. Additionally, the non-irritating nature of the film-forming spray (FFS) was affirmed through a histological study conducted on rat skin. Consequently, the KTZ-PNPs-based FFS emerges as a promising candidate for the treatment of topical fungal infections.

Graphical Abstract