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家族化合物的成员，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，它被认为可以防止氧化组织损伤。虽然它们在视网膜组织内的运输和浓度的确切机制尚不清楚，但外源性补充叶黄素已被证明可以增加黄斑内这些分子的浓度。鉴于黄叶素在黄斑和视网膜内积累，本申请建议使用叶黄素和玉米黄质作为载体分子，用于治疗黄斑和视网膜疾病的常规药物。为了评估叶黄素介导的药物传递的潜力，叶黄素和玉米黄质将与酮酸（一种非甾体抗炎药）或曲安奈德（一种类固醇药）进行化学连接。由此产生的相关化合物将在日本鹌鹑中进行积累测试，日本鹌鹑是一种已被证明用于叶黄素研究的动物模型。鹌鹑将被分为五个实验组，每组注射含有安慰剂、实验连接化合物、黄叶酚、常规药物或未连接的黄叶酚和药物的组合的溶液。随后，将通过高效液相色谱法测量视网膜、血清和其他组织中的药物和叶黄素水平，并分析所得数据，以确定叶黄素连锁是否会导致更好的药物靶向和传递到视网膜。

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.