Safety and in vivo release of fluconazole-loaded implants in rabbits' eyes

Abstract

Drug delivery to the eye cavity remains a challenge, owing to the ocular-blood barriers and rapid clearance of the drugs from aqueous humor and choroid. In order to overcome this problem, this study aimed to evaluate the ocular safety of fluconazole-loaded poly-lactide-co-glycolide implants (FL-PLGA implants). The concentration of fluconazole in the vitreous of rabbits'eye after FL-PLGA implants (25%w/w) application or intravitreal fluconazole suspension administration (1.8 mg/ml) was compared. At predefined periods, vitreous was collected and the concentration of fluconazole was assayed. In vitro tolerance of the implant was performed in ARPE-19 cells. The clinical evaluation of the rabbits'eyes that received FL-PLGA implants was realized during the 6 weeks of the study. Fluconazole was released from implants during 6 weeks, while the drug suspension injected into the eye was detected for 120 min. FL-PLGA implants were well tolerated in the eye, once no ocular abnormalities were clinically detected. The in vitro toxicity study revealed that devices did not induce alteration to ARPE-19 cells. Our results suggest that PLGA implants controlled fluconazole release for a prolonged period compared to the fluconazole suspension injected into the vitreous and showed ocular tolerance and in vitro biocompatibility.