Abstract

   Fungal keratitis (FK) remains a severe sight-threatening disease, and case management is difficult due to ocular intrinsic barriers and drug shortages. Econazole (ECZ), a broad-spectrum antifungal agent, is limited in ocular applications due to the poor water solubility and strong irritant property.  We successfully prepared solid-lipid nanoparticle-based ECZ eye drops (E-SLNs) by microemulsion method, and the physicochemical properties of E-SLNs were investigated. Corneal permeability, antifungal ability against Fusarium spp., irritation and bioavailability compared to ECZ Suspension (E-Susp) were evaluated in vitro and in vivo. E-SLNs were a uniform and stable system which had an average particle size of 19 nm and a spherical morphology. E-SLNs also exhibited controlled release, enhanced antifungal activity without irritation. The pharmacokinetic analysis in vivo confirmed that E-SLNs showed an improved ocular bioavailability and the drug concentration in the cornea were above minimum inhibitory concentration (MIC) for 3 h after single administration.