Intravaginal Gel for Sustained Delivery of Occidiofungin and Long-Lasting Antifungal Effects

Area of Science:

• Mycology
• Pharmacology
• Drug Delivery

Background:

• Fungal infections, particularly those caused by *Candida* species, pose significant health risks due to increasing antifungal resistance.
• Recurrent vulvovaginal candidiasis (RVVC) affects 5-9% of women, impacting both immunocompromised and immunocompetent individuals.
• Occidiofungin is a novel cyclic peptide antifungal with a broad spectrum and a unique fungicidal mechanism.

Purpose of the Study:

• To develop and characterize a novel gel formulation (OCF001) of occidiofungin for intravaginal application.
• To evaluate the drug release kinetics and efficacy of the occidiofungin gel formulation.
• To assess the safety of the occidiofungin gel formulation in preclinical models.

Main Methods:

• Utilized hydroxyethyl cellulose and hydroxypropyl β-cyclodextrin for gel formulation and occidiofungin solubilization.
• Employed Franz cells and LC-MS/MS to quantify drug diffusion rates through a skin-mimetic membrane.
• Conducted ex vivo mouse skin efficacy studies and repeat intravaginal administration safety studies in rabbits.

Main Results:

• The occidiofungin gel formulation demonstrated a reduced rate of drug diffusion across the tested membrane.
• The formulation maintained occidiofungin at inhibitory concentrations for 24 hours, supporting a single daily application.
• Safety assessments in rabbits indicated tolerability following repeat intravaginal administration.

Conclusions:

• The developed occidiofungin gel formulation (OCF001) is suitable for intravaginal drug delivery.
• This formulation enhances drug exposure and supports a convenient once-daily dosing regimen for RVVC treatment.
• OCF001 represents a potential new therapeutic option for managing vulvovaginal candidiasis, addressing the challenge of antifungal resistance.