Butea monosperma seed oil loaded ethosomal vesicular carrier and its hydrogel for vaginal candidiasis: QbD based development, in vitro and in vivo evaluation

Abstract Purpose Vaginal candidiasis (VC), a common recurrent gynaecological disorder affects almost 70% women. Development of resistance to antifungal 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 activity. Methods EVs, formulated by ethanol injection-sonication method used Phospholipon90G 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), PDI (Y2) and %EE (Y3), were taken as response variables. Results The size of optimized EVs was found to be 240.9nm, PDI was 0.326, %EE was 53.84%. FESEM and HR-TEM unveiled vesicles of rhombic dodecahedral shape with smooth, sealed structure. The EVs, incorporated into carbopol gel demonstrated non-Newtonian behavior. MIC determination by broth microdilution method revealed MIC of EVs and hydrogel to be 2.5 times less as compared to BMSO against C. albicans. Anti-candidal activities determined using agar well diffusion method demonstrated better zone of inhibition for hydrogel vis-à-vis BMSO. Pharmacodynamic evaluation manifested 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. Conclusion The results disclosed EVs and EV hydrogel to possess better antifungal activity vis-a-vis BMSO and can be explored as potential alternative herbal product for VC.