Ionic Liquid-Engineered Ibrexafungerp Citrate Cubosomal Gel for Candidiasis: Formulation, and In Vitro-In Vivo Characterization

This study aimed to develop an ionic-liquid-based formulation of ibrexafungerp citrate (IBX) incorporated into a cubosomal gel for the topical treatment of candidiasis. Cubosomal formulations were optimized using a 3² full factorial design with hydrogenated glyceryl monooleate (GMO) and Poloxamer 407 as critical formulation variables. The optimized IBX-IL-loaded cubosomes (IBX-ILC-11) were comprehensively characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), powder X-ray diffraction (P-XRD), and Fourier-transform infrared spectroscopy (FTIR), vesicle size, zeta potential, surface morphology, in vitro and in vivo antifungal activity. Synthesis of IBX-IL was optimized IBX Ionic liquids (IBX-IL IBX-IL-loaded cubosomes (IBX-ILC-11) demonstrated markedly enhanced encapsulation efficiency of 44.63 ± 1.87. MALs-6 exhibited a mean particle size of 152.5±5.68 nm and a high negative zeta potential -32.7 ± 3.68 mV, indicating excellent colloidal stability. In vitro antifungal activity demonstrated potent activity of IBXLC gel against candida glabrata, with a minimum inhibitory concentration (MIC) of 0.8±0.1μg/mL and a minimum fungicidal concentration (MFC) of 1.6±0.2 μg/mL. Similarly, the MIC and MFC of BXLC gel against Candida albicans were found to be 8.0±0.92 μg/mL and 15.62 ±1.68 μg/mL, respectively when compared to IBX and IBX-IL. Furthermore, IBXLC gel significantly inhibited fungal adhesion and biofilm formation in a dose-dependent manner, achieving complete biofilm inhibition at MFC within 48 h. IBXLC gel showed superior in vivo antifungal efficacy with complete healing and tissue regeneration, highlighting its potential as an effective topical nanocarrier system for the treatment of fungal infections. IBXLC gel demonstrated significantly enhanced antifungal activity against Candida albicans and Candida glabrata, along with potent antibiofilm efficacy. IBXLC gel have superior in vivo therapeutic performance, achieving complete healing and tissue regeneration. These findings indicate that the integration of ionic liquid technology with cubosomal nanocarriers represents a promising strategy for improving topical delivery and therapeutic outcomes of IBX in treatment of candidiasis.