Ocular Amphotericin B Delivery By Chitosan-modified Nanostructured Lipid Carriers For Fungal Keratitis Therapy

Context:Fungal keratitis,a corneal fungal infection of the eye caused mainly by Candida species,has become the leading cause of blindness resulting from corneal disease in China.Present limitations in the management of ophthalmic fungal infections include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure.Objective:The aim of this study was to construct amphotericin B(AmB)loaded,chitosan-modified,nanostructured lipid carriers(AmB-CH-NLC)for prolonged ocular application and for the improvement of the delivery of AmB to the ocular mucosa.Materials and methods:The AmB-CH-NLC was produced by the method of emulsion evaporationsolidification at low temperature.The particle size,zeta potential,and encapsulation efficiency,drug release behavior,and corneal penetration ability were performed in vitro and in vivo.Results and discussion:The prepared AmB-CH-NLC nanoparticles exhibited measured size of 185.4nm,zeta potential of 27.1 mV,and entrapment efficiency of 90.9%.Sustained drug release behavior was observed in vitro.The ocular pharmacokinetic study in vivo showed better bioavilability of AmB-CH-NLC.The corneal penetration study showed that the AmB-CH-NLC could successfully penetrate into the cornea with no obvious irritation to the rabbits' eyes.Conclusion:The results support that this novel nanomedicine could be a promising system for effective ocular delivery of amphotericin B for fungal keratitis therapy.