Development of a Luliconazole Nanoemulsion as a Prospective Ophthalmic Delivery System for the Treatment of Fungal Keratitis: In Vitro and In Vivo Evaluation

Luliconazole (LCZ), a novel imidazole drug, has broad-spectrum and potential antifungal effects, which makes it a possible cure for fungal keratitis; nevertheless, its medical use in ocular infections is hindered by its poor solubility. The purpose of this study was to design and optimize LCZ nanoemulsion (LCZ-NE) formulations using the central composite design-response surface methodology, and to investigate its potential in improving bioavailability following ocular topical administration. The LCZ-NE formulation was composed of Capryol 90, ethoxylated hydrogenated castor oil, Transcutol (R) P and water. The shape of LCZ-NE was spherical and uniform, with a droplet size of 18.43 +/- 0.05 nm and a low polydispersity index (0.070 +/- 0.008). The results of an in vitro release of LCZ study demonstrated that the LCZ-NE released more drug than an LCZ suspension (LCZ-Susp). Increases in the inhibition zone indicated that the in vitro antifungal activity of the LCZ-NE was significantly improved. An ocular irritation evaluation in rabbits showed that the LCZ-NE had a good tolerance in rabbit eyes. Ocular pharmacokinetics analysis revealed improved bioavailability in whole eye tissues that were treated with LCZ-NE, compared with those treated with LCZ-Susp. In conclusion, the optimized LCZ-NE formulation exhibited excellent physicochemical properties, good tolerance, enhanced antifungal activity and bioavailability in eyes. This formulation would be safe, and shows promise in effectively treating ocular fungal infections.

Automated summary

The study successfully designed and optimized LCZ nanoemulsion formulation with excellent bioavailability, antifungal activity, and ocular biocompatibility, showing promising potential in treating ocular fungal infections.