Central composite optimization of ocular mucoadhesive cubosomes for enhanced bioavailability and controlled delivery of voriconazole

This study aimed to formulate and statistically optimize cubosomal formulations loaded with voriconazole to enhance and control its ocular bioavailability. The independent variables of the employed central composite face-centered design were the percentages of monoolein and Pluronic F127. Particle size, zeta potential, drug content, entrapment efficiency and drug release parameters were adopted as dependent responses. The conducted factorial analysis resulted in an optimum formulation composed of 15% monoolein and 1.2% Pluronic F127. The optimum cubosomal formulation showed well-dispersed vesicles with a particle size of 160 nm and a relatively high drug loading (0.81%). Then, it was coated with chitosan to further enhance its precorneal residence time. The chitosan-coated formulation showed high mucoadhesive properties, in addition to being safe and biocompatible. Moreover, it showed higher Cmax, Tmax, AUC(0-8), AUC(0-∞), MRT, T1/2 and HVDt50%Cmax when compared to voriconazole suspension. It showed also higher concentration in the vitreous humor when compared to the drug suspension which indicates deeper penetration into the ocular tissue. Finally, the chitosan-coated optimum cubosomal formulation could be considered an efficient ocular nanocarrier for voriconazole.