Exploration of synergistically engineered invasomes of fluconazole incorporated with safranal against onychomycosis for enhanced transungual delivery

Drug Dev Ind Pharm. 2024 Dec;50(12):1031-1043. doi: 10.1080/03639045.2024.2437050. Epub 2024 Dec 8.

Abstract

Objective: The preparation of safranal-containing invasomes for fluconazole (FLU-IN) is investigated in the current research work to augment FLU permeation, bioavailability, and solubility via nail for transungual delivery.

Methods: FLU-IN was prepared utilizing the 'thin-film hydration process', and for optimization, 'Box-Behnken design (BBD)' was employed. Entrapment efficiency (EE), Poly-dispersity index (PDI), in vitro FLU release, vesicle size and zeta potential were used to characterize FLU-INopt. Confocal microscopy (CLSM), nail permeation investigation, and Transmission electron microscopy (TEM) were also carried out for further examination.

Results: The FLU-INopt demonstrated tiny, spherical, sealed-shape vesicles with a vesicle size of 140.3 nm, PDI of 0.1604, in vitro release of 84.32%, and entrapment efficiency of 74.65%. According to the CLSM investigation, the prepared formulation exhibits better FLU penetration over the nail than FLU suspension gel. Compared to the standard fluconazole marketed gel, the anti-fungal investigation showed that the FLU-IN gel has good anti-fungal potential against Trichophyton rubrum, Nakaseomyces glabrata and Candida albicans. Additional research on Wistar albino rats' skin irritancy supports the new FLU-IN formulation's safety for topical treatment.

Conclusion: The present study supported the claim that the developed invasomal formulation is a desirable vesicular carrier for FLU transungual delivery for the management of onychomycosis.

Keywords: Box-behnken design; Fluconazole; anti-fungal study; invasomes; onychomycosis.

MeSH terms

  • Administration, Topical
  • Animals
  • Antifungal Agents* / administration & dosage
  • Antifungal Agents* / pharmacokinetics
  • Antifungal Agents* / pharmacology
  • Biological Availability
  • Candida albicans / drug effects
  • Drug Delivery Systems / methods
  • Fluconazole* / administration & dosage
  • Fluconazole* / pharmacokinetics
  • Fluconazole* / pharmacology
  • Male
  • Nails* / drug effects
  • Nails* / metabolism
  • Nails* / microbiology
  • Onychomycosis* / drug therapy
  • Rats
  • Rats, Wistar*
  • Solubility
  • Terpenes / administration & dosage
  • Terpenes / chemistry

Substances

  • Fluconazole
  • Antifungal Agents
  • Terpenes