Nanosuspension as an Efficient Carrier for Improved Ocular Permeation of Voriconazole.

Abstract

The present limitations related to the ocular administration of antifungal drugs for the treatment of fungal keratitis include poor ocular bioavailability, limited retention time, and low ocular tissue penetration. This study aimed to prepare a novel ophthalmic voriconazole-loaded nanosuspension based on Eudragit RS 100. Pharmasolve® was explored as a corneal permeation enhancer in voriconazole ophthalmic formulation using in vitro and in vivo experiments. Briefly, 1% voriconazole-loaded nanosuspension was prepared using the quasi-emulsion solvent evaporation process. Characterizations of the voriconazole-loaded nanosuspension by Zetasizer Nano ZS and Transmission Electron Microscope (TEM) showed a uniform spherical shape without any agglomeration. The well-discreted nanoparticle with a size of 138 ± 1.3 nm was achieved with high entrapment efficiency (98.6 ± 2.5%) and positive zeta potential in the range of 22.5-31.2mV, indicating excellent physical stability. Voriconazole-loaded nanosuspension containing the penetration enhancer displayed good permeability both in vitro and in vivo compared with the commercial voriconazole injection. The voriconazole-loaded nanosuspension exhibited good antifungal activity, significantly inhibiting the growth of Candida albicans at a lower concentration of voriconazole (2.5μg/mL, p < 0.05). In conclusion, the voriconazole-loaded nanosuspension containing Pharmasolve® can be used as an effective ophthalmic formulation for the topical ocular delivery of voriconazole.