Butea monosperma Seed Oil Loaded Ethosomal Vesicular Carrier and Its Hydrogel for Vaginal Candidiasis: QbD Based Development, In Vitro and In Vivo Evaluation.

Vaginal candidiasis (VC), a common recurrent gynaecological disorder affects almost 70% of women. Development of resistance to anti-fungal agents exacerbates the need for new treatments against Candida infections. The objective of the current work was to develop ethosomal vesicles (EVs) and EV hydrogel of Butea monosperma seed oil (BMSO) for treatment of vaginal candidiasis, as BMSO has demonstrated fungicidal and bactericidal activities. EVs, formulated by ethanol injection-sonication method, used Phospholipon®90G and ethanol as excipients and were optimized by Box-Behnken design (BBD). BMSO (X₁), phospholipid (X₂) and ethanol concentration (X₃) were selected as input variables, while vesicle size (Y₁), polydispersity index (PDI) (Y₂) and percent entrapment efficiency (%EE) (Y₃) were taken as response variables. The size of optimized EVs determined by dynamic light scattering technique was found to be 249 ± 2.6 nm; PDI was 0.301 ± 0.013; %EE determined by high-speed centrifugation method was 53.84 ± 1.98%. Field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HR-TEM) unveiled vesicles of rhombic dodecahedral shape with smooth, sealed structure. The EVs, incorporated into carbopol gel, demonstrated non-Newtonian behaviour on a rotary type rheometer. Minimal inhibitory concentration (MIC) determination by broth microdilution method revealed MIC of EVs and hydrogel to be 2.5 times less, as compared to BMSO against Candida albicans (C.albicans). Anti-candidal activities determined using agar well diffusion method demonstrated better zone of inhibition for hydrogel vis-a-vis BMSO. Pharmacodynamic evaluation conducted on Balb/c female mice manifested a comparable decrease in fungal burden by EVs and EV hydrogel to marketed clotrimazole. Histopathology of vaginal tissue of treated groups showed no or mild inflammation with normal skin structure. The results disclosed EVs and EV hydrogel to possess better anti-fungal activity vis-a-vis BMSO and can be explored as potential alternative herbal product for VC. [ABSTRACT FROM AUTHOR]