Innovative antifungal therapy using Brij®-capped flexosomes loaded with Aripiprazole for Candida albicans associated vaginal infection

Aim and background This study aimed to investigate Aripiprazole (ARP) as a repurposed antifungal drug within Brij®-Capped flexosomes (O-FLs) mucoadhesive gel against vaginal candidiasis.Methods ARP-FLs prepared by thin-film hydration was optimized using a 23 factorial design to evaluate the effects of Edge Activator (EA) (X1), phospholipid amount (X2) (mg), and cationic surfactants (X3) on entrapment efficiency (EE%; Y1), particle size (PS; Y2), polydispersity index (PDI; Y3), and zeta potential (ZP; Y4). The best ARP-FLs were identified for optimization using Design-Expert® software. Brij®52 was utilized as a capping agent for the optimum formulation (O-FLs).Results The O-FLs demonstrated EE% of 95.61 % ± 0.49 %. Additionally, PS of 80.45 ± 2.13 nm, PDI of 0.444 ± 0.001, alongside ZP value of 33.05 ± 2.55 mV. O-FLs exhibited stability over a period of 90 days. Transmission electron microscopy revealed spherical vesicles. Confocal laser scanning microscopy demonstrated that the fluoro-labeled O-FLs were effectively deposited in the vagina. Further, O-FLs were incorporated into a mucoadhesive gel for improving its retention. Data from the ex-vivo permeation experiments revealed a remarkably lower permeability for the O-FLs gel relative to other tested formulations. Furthermore, in-vivo evaluations verified that the developed O-FLs gel was highly effective against Candida albicans. Lastly, histopathological assessments confirmed the safety profile of the administered O-FLs gel.Conclusion These insights highlight the promising platform of utilizing O-FLs gel as an effective system for repurposed ARP to treat vaginal candidiasis.