<p>Voriconazole is known to be an effective therapeutic agent for fungal infections, such as cryptococcal meningitis which is commercially available in both oral and intravenous administrations. In this study, the voriconazole-loaded nanoemulsion formation was developed to deal with limitations of existing formulations and aimed towards enhancing the brain delivery via nasal administration for the treatment of cryptococcal meningitis. The selection of the optimal composition of oleic acid, Tween 80, and Transcutol P as oil phase, surfactant, and co-surfactant was performed using pseudo-ternary phase diagrams. The results of physicochemical characterization presented that the selected formulations displayed small droplet size, low polydispersity, adequate zeta potential, etc. The high %encapsulation efficiency (93.53 to 97.65%) of the nanoemulsion formulations was observed. The nanoemulsions also showed good physical stability under different stress conditions. The release study showed the rapid release behavior of the formulation with about 97.57% of cumulative drug release after 120&#xa0;min exhibited by optimized formulation. Additionally, cytotoxicity assessment revealed no adverse effects on nasal epithelial cells, indicating the safety of the optimized formulation. The nanoemulsion formulation showed zones of inhibition considerably larger than the blank nanoemulsion and voriconazole solution against <i>Candida albicans</i>. These outcomes underscore the prospect of the developed nanoemulsion as a non-invasive and effective treatment option for fungal infections, offering advantages over conventional oral and intravenous formulations.</p> Graphical Abstract <p></p>

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Development and In Vitro Characterization of a Voriconazole Loaded Nanoemulsion for Potential Intranasal Drug Delivery

  • Himanshu Paliwal,
  • Bhupendra G. Prajapati

摘要

Voriconazole is known to be an effective therapeutic agent for fungal infections, such as cryptococcal meningitis which is commercially available in both oral and intravenous administrations. In this study, the voriconazole-loaded nanoemulsion formation was developed to deal with limitations of existing formulations and aimed towards enhancing the brain delivery via nasal administration for the treatment of cryptococcal meningitis. The selection of the optimal composition of oleic acid, Tween 80, and Transcutol P as oil phase, surfactant, and co-surfactant was performed using pseudo-ternary phase diagrams. The results of physicochemical characterization presented that the selected formulations displayed small droplet size, low polydispersity, adequate zeta potential, etc. The high %encapsulation efficiency (93.53 to 97.65%) of the nanoemulsion formulations was observed. The nanoemulsions also showed good physical stability under different stress conditions. The release study showed the rapid release behavior of the formulation with about 97.57% of cumulative drug release after 120 min exhibited by optimized formulation. Additionally, cytotoxicity assessment revealed no adverse effects on nasal epithelial cells, indicating the safety of the optimized formulation. The nanoemulsion formulation showed zones of inhibition considerably larger than the blank nanoemulsion and voriconazole solution against Candida albicans. These outcomes underscore the prospect of the developed nanoemulsion as a non-invasive and effective treatment option for fungal infections, offering advantages over conventional oral and intravenous formulations.

Graphical Abstract