In vitro and in vivo evaluation of cubosomal nanoparticles as an ocular delivery system for fluconazole in treatment of keratomycosis.

The objective of the present study was to enhance ocular antifungal activity of fluconazole (FCZ) in treatment of keratomycosis through incorporation into cubosomal nanoparticles. FCZ-loaded cubosomal dispersions were prepared by emulsification method according to 23 full factorial design. Design-Expert® software was used to study the effects of different formulation factors on properties of FCZ-loaded cubosomal dispersions and select the optimal formulation. Eight FCZ-loaded cubosomal dispersions were prepared and were in vitro and in vivo evaluated. In vitro, the results revealed that the optimum formula exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 85.70 ± 2.56% of FCZ. The ex vivo permeation study confirmed a two-fold enhancement in FCZ permeation through rabbit cornea compared to aqueous FCZ solution. Furthermore, in vivo ocular tolerance and histopathological studies proved the efficacy and safety FCZ-loaded cubosomal dispersion in treatment of induced keratomycosis in rats compared to aqueous FCZ solution after topical ocular application. In conclusion, the obtained results indicated that cubosomes could be promising ocular drug delivery system for enhancing antifungal activity of FCZ in treatment of fungal keratitis in rats. Graphical abstract.