XANTHOPHYLL-MEDIATED RETINAL DRUG DELIVERY

说明(申请人提供)：叶黄素和玉米黄质是类胡萝卜素家族的成员，由植物和微生物合成，在其中具有色素和光保护作用。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，人类的视网膜含有大量的叶黄素，据信可以防止氧化组织损伤。尽管它们在视网膜组织内的转运和浓度的确切机制仍然不清楚，但外源性补充叶黄素已被证明增加了这些分子在黄斑内的浓度。鉴于叶黄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常规药物的载体分子，用于治疗黄斑和视网膜疾病。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在化学上与非类固醇抗炎药酮咯酸或类固醇曲安奈德联系在一起。然后，将测试得到的关联化合物在日本鹌鹑体内的蓄积情况，这是叶黄素研究的一个经过验证的动物模型。将把鹌鹑分成五个试验组，每个试验组注射含有安慰剂、实验关联化合物、叶黄素、常规药物或非关联叶黄素和药物组合的溶液。随后将用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，并对结果数据进行分析，以确定叶黄素联系是否会导致更好的药物靶向和视网膜递送。

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.