In Vitro and In Vivo Release Characteristics of Tacrolimus (FK506) from an Episcleral Drug-Delivery Implant

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PURPOSE: To investigate the in vitro and in vivo release characteristics of Tacrolimus (FK506) from an episcleral drug-delivery implant. METHODS: For in vitro experiments, Tacrolimus-loaded implants (0.5 mL; at concentrations of 0.25, 0.5, and 1.0 mg/mL) were immersed in a balanced salt solution. Samples of the surrounding liquid were aspirated at different times over a 96-h period. For in vivo experiments, the experimental group received an implant loaded with Tacrolimus (0.5 mg/mL; 0.5 mL); the control group was given a subconjunctival injection of 0.5 mL Tacrolimus (0.5 mg/mL). On postoperative days 3, 7, 14, 28, and 56, 3 animals were sacrificed, and their eyes were enucleated. Tacrolimus concentrations were determined by liquid chromatographic-tandem mass spectrometry. Ocular toxicity was evaluated by slit-lamp photography, fundus photography, intraocular pressure (IOP), and histology. RESULTS: The implants released Tacrolimus in a biphasic pattern for 96 h in the in vitro study. The release kinetics were not dependent on the drug concentrations. The in vivo study showed statistically significant differences between the 2 treatment groups. Tacrolimus levels were particularly high in the conjunctiva, iris, ciliary body, cornea, sclera, choroid, and retina in the experimental group, while concentrations were low and only lasted for 1 week in the controls. Slit-lamp photography, fundus photography, IOP, and histology showed no evidence of toxic effects. CONCLUSIONS: The episcleral drug-delivery implant mechanically released Tacrolimus through the apertures of capsules and, consequently, may be a promising drug vehicle for the treatment of immune-mediated ocular disorders.