INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The E-SLNs colloid system is a promising therapeutic approach for fungal keratitis and could serve as a candidate strategy for other ocular diseases.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The E-SLNs colloid system is a promising therapeutic approach for fungal keratitis and could serve as a candidate strategy for other ocular diseases.
Authors: Victoria Díaz-Tomé; Andrea Luaces-Rodríguez; Jesús Silva-Rodríguez; Sara Blanco-Dorado; Laura García-Quintanilla; José Llovo-Taboada; José Blanco-Méndez; Xurxo García-Otero; Rubén Varela-Fernández; Michel Herranz; María Gil-Martínez; María Jesús Lamas; Miguel González-Barcia; Francisco J Otero-Espinar; Anxo Fernández-Ferreiro Journal: J Pharm Sci Date: 2018-01-03 Impact factor: 3.534
Authors: João Barroso; Uwe Pfannenbecker; Els Adriaens; Nathalie Alépée; Magalie Cluzel; Ann De Smedt; Jalila Hibatallah; Martina Klaric; Karsten R Mewes; Marion Millet; Marie Templier; Pauline McNamee Journal: Arch Toxicol Date: 2016-03-21 Impact factor: 5.153