LIPOSOMAL INTEROCUL. DRUG DELIVERY IN VITRO AND IN VIVO

脂质体眼内。

• 批准号: 3258318
• 负责人: SIDNEY LERMAN
• 金额: $ 8.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3258318
• 关键词: aldehyde reductase; antibiotics; autoradiography; cataract; cytotoxicity; doxorubicin; drug delivery systems; drug vehicle; electron microscopy; eye agent; eye pharmacology; fluorescence microscopy; fluorescence spectrometry; histology; human tissue; lens; lens proteins; lipids; liposomes; nonvisual photosensitivity; nuclear magnetic resonance spectroscopy; oxidoreductase inhibitor; phosphorescence; psoralens; radioprotective agents; radiotracer; scintillation counter; ultrasonography; ultraviolet spectrometry

Lectin-mediated binding of liposomes and delivery of specific agents by this means to the ocular lens, cornea and other intraocular tissues will be investigated. Whole eyes and human, rabbit and rat ocular tissues will be used for in vitro studies and rabbits will be employed for in vivo experiments. Liposomes will be prepared from various lipid (and glycolipid) and fluorescein-labelled lectin combinations to assess the effects of liposomal charge on binding of lectin to the vesicles and on the binding of liposome-lectin complexes to ocular tissues. The effects of vesicle size and form on binding, trapping efficiency, tissue distribution, and intraocular pressure will also be evaluated. Binding will be assayed in vitro and in vivo by fluorescence microscopy (FM), and scanning and transmission electron microscopy. The fate of liposomes bound to ocular tissues over specific time intervals will also be evaluated. The effects of inclusion of cholesterol and dipalmitoylphosphatidyl-labelled compounds will be assessed by fluorescence spectroscopy and liquid scintillation counting of external aqueous phases of liposome suspensions at different time intervals. Intracellular and intratissue delivery of fluorescent markers by liposomes will be studied by FM, fluorescence spectroscopy and UV-visible slit lamp densitography. Delivery of isotope labelled markers will be analyzed by autoradiography and liquid scintillation counting of tissue homogenates. Liposomal delivery of 8-methoxypsoralen will be assessed by phosphorescence and EPR spectroscopy and other techniques. Free radical scavengers and aldose reductase inhibitors will be delivered to the ocular lens in vivo to evaluate their ability to protect the lens from the development of radiation and sugar cataracts, respectively, and any dose-response phenomena associated with them. Liposomally encapsulated pilocarpine and nucleic acid analogues will be applied to the cornea in vivo and the effects of liposomal delivery on diffusion of drugs across the cornea and on drug activity on the cornea itself will be evaluated. Pilot studies will also be carried out to assess the feasibility of using liposomally encapsulated proteolytic enzymes to lyse cataracts in situ.

凝集素介导的脂质体结合，并通过 这意味着眼镜，角膜和其他眼内组织 调查。 整个眼睛和人类，兔子和大鼠眼组织将是 用于体内的体外研究和兔子用于体内 实验。 脂质体将从各种脂质中制备（和 糖脂）和荧光素标记的凝集素组合，以评估 脂质体电荷对凝集素与囊泡结合的影响以及 脂质体肌肉蛋白复合物与眼组织的结合。 效果 囊泡大小和结合，捕获效率，组织分布的形式， 还将评估眼内压。 绑定将被分析 体外和体内通过荧光显微镜（FM）以及扫描和 透射电子显微镜。 脂质体的命运与眼睛结合 在特定时间间隔内的组织也将进行评估。 效果 包括胆固醇和二硫二酰磷脂酰标记的化合物 将通过荧光光谱和液体闪烁来评估 在不同的脂质体悬浮液的外水相计数 时间间隔。 荧光的细胞内和静脉内输送 FM，荧光光谱和 紫外可见的缝隙光密摄影。 同位素标记的标记 将通过放射自显影和液体闪烁计数来分析 组织匀浆。 8-甲氧基索拉伦的脂质体递送将是 通过磷光和EPR光谱和其他技术评估。 将输送自由基清除剂和醛降低抑制剂 到体内眼镜镜头以评估其保护镜头的能力 分别来自辐射和糖白内障的发展，以及 与它们相关的任何剂量反应现象。 脂质体封装 毛果石和核酸类似物将被应用于角膜 体内和脂质体递送对药物扩散的影响 将评估角膜和角膜本身的药物活性。 飞行员 还将进行研究以评估使用的可行性 脂质体封装的蛋白水解酶原位裂解白内障。