Synergistic Liposomal Delivery of Ibrexafungerp Citrate and Marine-Sourced Silver Nanoparticles for Effective Management of Vulvovaginal Candidiasis

Background: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the targeted treatment of vulvovaginal candidiasis (VVC), employing green-synthesized silver nanoparticles (AgNPs) derived from Ascophyllum nodosum (AN) and incorporating ibrexafungerp citrate (IBC) into a liposomal formulation. Methods: AgNPs were biosynthesized using AN extract and characterized. Liposomes were prepared by thin-film hydration, and optimised using Central Composite design and characterized and optimized. Optimised liposomes, co-loaded with IBC and AN-AgNPs, were incorporated into a Carbopol-CMC-based topical gel. Results: FTIR shifts in the –OH (3332.31 cm⁻¹) and carbonyl (1636.87 cm⁻¹) bands with reduced intensity confirmed their involvement in Ag⁺ reduction and nanoparticle surface coordination, while the persistence of the 1015 cm⁻¹ band indicated the role of polysaccharides in capping and stabilizing the AN-AgNP. Characterization of the optimized liposomes (IBCL-11) revealed a particle size of 127.2 nm, a zeta potential of −43.8 mV, and a polydispersity index (PDI) of 0.35. Transmission Electron Microscopy (TEM) confirmed the presence of intact, spherical vesicles, while Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) validated the molecular dispersion and amorphous characteristics of the films. In vitro evaluations of the IBC liposomal gel demonstrated a sustained drug release of 72.6% over 24 h, alongside enhanced drug penetration across all skin layers. Antifungal assays highlighted the formulation’s potent efficacy, yielding Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values below 1 µg/mL. Furthermore, the treatments exhibited strong anti-biofilm properties; at MIC and MBC levels, AN-AgNPs achieved biofilm reductions of 45.27 ± 3.16% and 27.62 ± 2.13%, respectively, whereas IBCL-11 produced reductions of 34.25 ± 2.43% and 16.28 ± 1.72%. Conclusion: Ultimately, this study successfully developed an eco-friendly liposomal formulation co-loaded with AN-AgNPs and IBC, offering a promising and targeted therapeutic approach for the treatment of vulvovaginal candidiasis.