XANTHOPHYLL-MEDIATED RETINAL DRUG DELIVERY

叶黄素介导的视网膜药物递送

• 批准号: 6670771
• 负责人: DENNIS Michael MARCUS
• 金额: $ 12.88万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6670771
• 关键词: bioaccumulation; carotenoids; chemical conjugate; drug delivery systems; high performance liquid chromatography; nonsteroidal antiinflammatory agent; quail; retina; technology /technique development; triamcinolone

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.

描述（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，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被证明可以增加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聚，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输送的潜力，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（一种类固醇）进行化学连接。 然后将测试所得连接化合物在日本鹌鹑中的积累情况，日本鹌鹑是叶黄素研究的经过验证的动物模型。 鹌鹑将被分为五个实验组，每个实验组都注射含有安慰剂、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，并对所得数据进行分析，以确定叶黄素连接是否会导致更好的药物靶向和递送到视网膜。