XANTHOPHYLL-MEDIATED RETINAL DRUG DELIVERY

描述（由申请人提供）：叶黄素和玉米黄质是类胡萝卜素化合物家族的成员，由植物和微生物合成，其中它们具有色素沉着和光保护作用。 当类胡萝卜素含有一个或多个氧原子时，如叶黄素和玉米黄质，它们被称为叶黄素。有趣的是，人类视网膜含有大量的叶黄素，据信这可以防止氧化性组织损伤。 虽然它们在视网膜组织内的运输和浓度的精确机制仍然不清楚，但外源性补充叶黄素已显示出增加黄斑内这些分子的浓度。 鉴于叶黄素在黄斑和视网膜内积累，本申请提出使用叶黄素和玉米黄质作为用于治疗黄斑和视网膜疾病的常规药物的载体分子。 为了评估叶黄素介导的药物递送的潜力，叶黄素和玉米黄质将与酮咯酸（一种非甾体抗炎药）或曲安西龙（一种甾体）化学连接。 然后，将测试所产生的连接化合物在日本鹌鹑中的累积，日本鹌鹑是叶黄素研究的经证实的动物模型。 将鹌鹑分为五个实验组，每组注射含有安慰剂、实验连接化合物、叶黄素、常规药物或未连接叶黄素和药物的组合的溶液。随后通过高效液相色谱法测量视网膜、血清和其它组织中的药物和叶黄素水平，并分析所得数据以确定叶黄素连接是否导致上级药物靶向和递送至视网膜。

DESCRIPTION (provided by applicant): 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.