Enhanced Skin Penetration and Clinical Antifungal Activity of Eugenol Encapsulated in Aspasomes

Fungal infections are among the common diseases affecting the skin, which necessitate either topical or systemic delivery of antifungal agents. Eugenol was reported to exhibit antifungal properties, but owing to its poor skin-penetration ability, it requires encapsulation within delivery carriers. This study aimed to enhance the skin penetration and antifungal efficacy of eugenol through encapsulation in novel aspasomal formulations. Cationic and anionic aspasomes were prepared using ascorbyl palmitate, transcutol, and charge inducers, achieving high encapsulation efficiencies (90.55% for cationic, 63.32% for anionic) and stable formulations. <i>Ex-vivo</i> skin deposition studies showed significant eugenol retention in deeper skin layers, with 82.2% (cationic) and 77.2% (anionic) total skin deposition. Both formulations demonstrated superior antifungal activity compared to eugenol solution, with larger zones of inhibition against <i>Candida albicans</i> and <i>Trichophyton rubrum</i>. Clinical trials in patients with candidiasis and dermatophytosis revealed complete resolution of symptoms in 100% of patients treated with aspasomes, while eugenol solution showed partial improvement. These findings suggest that aspasomal encapsulation significantly enhances eugenol’s therapeutic potential, offering a promising strategy for improving the treatment of fungal skin infections.