Retinal toxicity of intravitreally injected plain and liposome formulation of fluconazole in rabbit eye.
OBJECTIVE
Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against Candida albicans in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection.


METHODS
Twelve New Zealand albino rabbits weighing 2-2.5 kg were used. Two rabbits were used for every dose level. Liposome formulation containing 100 and 200 microg of fluconazole in sterile phosphate buffer solution and plain fluconazole at concentrations of 100, 200, 400 and 800 microg in 0.1 ml of sterile normal saline were injected intravitreally into the right eyes. The left eyes received 0.1 ml normal saline or 0.1 ml of liposome formulation without fluconazole. One week later, the animals were sacrificed, their eyes enucleated and processed for light microscopy and scanning electron microscopy.


RESULTS
It showed that plain fluconazole at a concentration of 100 microg and above caused retinal changes, with disorganization of the photoreceptor outer segments. However, liposome formulation of fluconazole (200 microg/0.1 ml) did not show any significant microscopic changes of the retina.


CONCLUSIONS
The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 microg/0.1 ml.
Velpandian
Thirumurthy
T
Ocular Pharmacology Division, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. tvelpandian@hotmail.com
Narayanan
Kanniapan
K
Nag
Tapas Chandra
TC
Ravi
Alok Kumar
AK
Gupta
Suresh Kumar
SK
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D009877:Endophthalmitis / Q000188:drug therapy; D015821:Eye Infections, Fungal / Q000188:drug therapy; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000633:toxicity*; D007267:Injections; D008081:Liposomes; D008297:Male; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000648:ultrastructure*; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology; D012307:Risk Factors; D014822:Vitreous Body
D000935:Antifungal Agents; D008081:Liposomes; D015725:Fluconazole