Purchase this article with an account.
LP J Cruysberg, C Hejny, RM M A Nuyts, DH Geroski, F Hendrikse, HF Edelhauser; In Vivo Transscleral Drug Delivery of Fluorescein Labeled Dexamethasone and Methotrexate with a Fibrin Sealant Depot . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2302.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Delivering drugs to the posterior ocular tissues across the sclera may avoid possible complications associated with intraocular delivery and provide localized sustained-release delivery. Purpose: To evaluate the in vivo transscleral delivery of dexamethasone and methotrexate with a fibrin sealant depot. Method: Dutch-belted rabbits (n=21) received a unilateral subconjunctival injection containing fluorescein-labeled dexamethasone or methotrexate, either in fibrin sealant (Haemacure) or in BSS. A serum sample and an aqueous sample of both the injected and the opposite eye were obtained at 2, 48, and 336 hours. At various intervals after injection, rabbits were sacrificed. Their eyes were enucleated and instantly frozen in dry ice and acetone. The frozen eyes were dissected and the tissues were then divided into vitreous, choroid and retina, sclera, cornea and remaining fibrin sealant bleb. The tissue was extracted in a small amount of BSS (1 ml), and fluorescence was measured with a spectrofluorometer. Results: None of the injected eyes appeared to be inflamed at the time of enucleation. The bleb containing the drug in fibrin sealant was still clearly visible at 2 weeks. Highest intraocular concentrations were reached 2 hours after injection, for both dexamethasone and methotrexate in either vehicle. Two weeks after the initial injection intraocular concentrations in the choroid and retina were approximately two (245 ng/ml vs. 139 ng/ml; for dexamethasone) to five (582 ng/ml vs. 130 ng/ml; for methotrexate) fold higher in fibrin sealant vehicle as compared to the BSS vehicle. Vitreal concentrations measured at 2 weeks were approximately two fold higher (dexamethasone: 25 vs. 12 ng/ml; methotrexate: 48 vs. 20 ng/ml) when the drugs were delivered in fibrin sealant. Conclusion: Delivering dexamethasone and methotrexate to the eye with fibrin sealant appears to sustain higher intraocular concentrations over a longer period of time. These experiments suggest that fibrin sealant could be used as an effective method for transscleral sustained drug delivery to the intraocular tissues of the eye.
This PDF is available to Subscribers Only