Lutein and zeaxanthin are members of the carotenoid family of compounds and are synthesized by plants and microorganisms, in which they have pigmentation and photoprotective roles. When carotenoids contain one or more oxygen atoms, as in lutein and zeaxanthin, they are known as xanthophylls. Interestingly, the human retina contains significant quantities of xanthophylls, which are believed to prevent oxidative tissue injury. Though the precise mechanism of their transport and concentration within retinal tissue remains obscure, exogenous supplementation of xanthophylls has been shown to increase the concentration of these molecules within the macula. Given that xanthophylls accumulate within the macula and retina, this application proposes to use lutein and zeaxanthin as carrier molecules for conventional medications used in the treatment of macular and retinal diseases. To evaluate the potential of xanthophyll-mediated drug delivery, lutein and zeaxanthin will be chemically linked to ketorolac, a non-steroidal anti- inflammatory drug, or triamcinolone, a steroid. The resulting linked compounds will then be tested for accumulation in Japanese quail, a proven animal model for xanthophylls studies. Quail will be divided into five experimental groups, each to be injected with solutions containing placebo, experimental linked compounds, xanthophylls, conventional drugs, or a combination of unlinked xanthophylls and drugs. Drug and xanthophyll levels in retina, serum, and other tissues will subsequently be measured by high-performance liquid chromatography and the resulting data analyzed to determine whether xanthophyll linkage results in superior drug targeting and delivery to the retina.
