Ocular amphotericin B delivery by chitosan-modified nanostructured lipid carriers for fungal keratitis-targeted therapy.
BACKGROUND
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 targeted delivery of AmB to the ocular mucosa.


METHODS
The AmB-CH-NLC was produced by the method of emulsion evaporation-solidification 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.


CONCLUSIONS
The prepared AmB-CH-NLC nanoparticles exhibited a measured size of 185.4 nm, a zeta potential of 27.1 mV, and an entrapment efficiency of 90.9%. Sustained drug release behavior was observed in vitro. The in vivo ocular pharmacokinetic study indicated improved bioavailability 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.


CONCLUSIONS
The results support that this novel nanomedicine could be a promising system for effective ocular delivery of amphotericin B for fungal keratitis-targeted therapy.
a Department of Ophthalmology , Medical college of Nanchang University , Nanchang , Jiangxi , China.|b Department of Ophthalmology , Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University , Shaoxing , Zhejiang , China.
Tian
T
Fu
c Department of Ophthalmology , Affiliated Eye Hospital of Nanchang University, Jiangxi Research Institute of Ophthalmology and Visual Sciences, Nanchang University , Nanchang , Jiangxi , China , and.
Jinglin
J
Yi
d Department of Ophthalmology , Tongde Hospital of Zhejiang Province , Hangzhou , Zhejiang , China.
Songyi
S
Lv
d Department of Ophthalmology , Tongde Hospital of Zhejiang Province , Hangzhou , Zhejiang , China.
Bing
B
Zhang
D060433:Administration, Ophthalmic; D000666:Amphotericin B / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000378:metabolism; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004655:Emulsions; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000378:metabolism; D007634:Keratitis / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011817:Rabbits
D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D008055:Lipids; D008081:Liposomes; D000666:Amphotericin B; D048271:Chitosan
Amphotericin B; bioavailability; chitosan; lipid nanoparticles; ocular delivery