VRS '99: Sustained Drug Delivery Systems

Abstract Vitreoretinal Symposium Marburg - Frankfurt 1999

Sustained Drug Delivery Systems

Glenn J. Jaffe, M.D.
Durham

Currently available common drug delivery methods include topical, periocular, and systemic routes of administration. Topical and systemic therapy depend on patient compliance to administer the medications. With all of these methods, drug levels cannot be maintained at a constant level and the limited duration of action and inadequate intraocular penetration may limit the drug's effectiveness. Furthermore, side effects may be treatment limiting. Sustained drug delivery systems can overcome many of the disadvantages of topical, periocular, and systemic therapy. Compliance is not a factor since the drug delivery device is surgically implanted into the eye. With sustained drug delivery devices, it is possible to achieve constant drug levels over a prolonged period of time. Furthermore, it is possible to deliver the drug directly to the site of pathology. Sustained drug delivery devices may be biodegradable (e.g., polylactic polyglycolic acid polymers) or nonbiodegradable (e.g., ethelene vinyl acetate and polyvinyl alcohol). Recently, we have investigated a variety of drug delivery devices to treat intraocular inflammation and proliferative vitreoretinopathy. We have constructed sustained drug delivery devices consisting of cyclosporine and corticosteroids (dexamethasone and fluocinolone) which have been used to effectively treat uveitis in experimental models, and to a limited extent, in humans. A codrug consisting of a corticosteroid covalently linked to 5-fluorouracil has also been tested in an experimental model of proliferative vitreoretinopathy and subretinal neovascularization. The codrug itself is inactive but breaks down into its active components in an aqueous environment. The codrug very effectively suppressed retinal detachment in a model of proliferative vitreoretinopathy and also effectively inhibited angiogenesis in an experimental model of subretinal neovascularization. Sustained drug delivery systems show great promise in the management of a variety of ocular diseases and, in the future, may replace some of the currently available delivery methods.

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