Ketoprofen-loaded quatsomes as a smart repurposed antifungal therapy for vaginal infections: formulation,...

Vulvovaginal candidiasis (VVC) is one of the most common fungal infections requiring more effective and patient-friendly therapies. This study introduces repurposed Ketoprofen (KPN) Quatsomes (QS) as a novel nano-platform for localized antifungal treatment.

KPN-QS were prepared using quaternary ammonium surfactants and cholesterol via probe sonication and optimized through a 3¹ × 2² mixed factorial design using Design-Expert^® software. The effects of quaternary ammonium surfactant type (factor A), amount of vesicle-forming materials (factor B), and cholesterol-to-surfactant ratio (factor C) were evaluated to maximize entrapment efficiency and zeta potential, while minimizing particle size.

The optimized QS exhibited spherical nano-sized vesicles (113.7 nm) with high entrapment efficiency (96.8%) and strong positive zeta potential (72.5 mV), ensuring stability and enhanced mucosal adhesion. TEM confirmed the spherical morphology, and in vitro release showed biphasic behaviour with 86.5% release after 8 h, alongside excellent storage stability. Repurposing KPN as an antifungal agent significantly enhanced both in vitro and in vivo microbiological efficacy. The formulation displayed promising MIC values against Candida albicans and markedly improved antifungal performance in vivo VVC model. The KPN-QS group exhibited 4.807 and 2.941 log reductions in fungal count compared to the negative control and KPN suspension, respectively, with complete eradication in three rats after 72 h. Histopathological analysis confirmed the safety of QS on vaginal mucosa.

Collectively, repurposed KPN-QS constitute a stable, biocompatible nanocarrier for targeted vaginal delivery, demonstrating superior antifungal activity and therapeutic potential in VVC.