Voriconazole and Beauvercin Loaded Niosomal Mucoadhesive Nanogel as an effective Treatment for the Management of Oral Candidiasis

Abstract

Oral candidiasis is a fungal infection, which affects the oral mucosa. The main causative agent of this is Candida albicans and as the literature indicates highest prevalence of Candida bloodstream infections in India. Most commonly azole derivatives such as miconazole, fluconazole, itraconazol etc. are used to manage the infection. However, their efficacy is compromised due to multidrug resistance. A new azole derivative voriconzole could be effective but its poor water solubility and bioavailability are seen as significant limitations. Its efficacy can be enhanced by combining it with beauvericin, a cyclic hexadepsipeptide with remarkable antifungal activity against candida. One study reported that combining of beauvericin with voriconzole reduce the MIC of voriconazole by 128th times. Furthermore the solubility and bioavailability were enhanced by loading both the drugs in niosomes. The niosomes were imcorporated into a polymeric mucoadhesive gel post statistically optimization by the Box-Behnken experimental design. The niosomes were subjected to evaluation for vesicular size, surface morphology, entrapment efficiency, drug release and zeta potential High entrapment efficiency was observed in the optimized noisome formulation F3 (89.89±0.64 % for voriconazole and 92.98±0.35 % for beauvericin) exhibiting cumulative drug release of 79.98±1.87 % for voriconazole and 69.17±1.98 % for beauvericin. The mucoadhesive gel was smooth, homogenious with desired pH and mucodhesion. The stability studies indicated that all the formulations are stable as evidence by no significant change in drug content over the time. These findings suggest that a niosmal mucoadhesive gel loaded with voriconazole and beauvericin is a good therapeutic delivery system for the effective treatment of oral candidiasis.