权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Design of Cyclodextrin Derivatives as Artificial Lipid Carriers that are not Receptor-directed

环糊精衍生物作为非受体定向的人工脂质载体的设计

基本信息

批准号：
05671873
负责人：
IRIE Tetsumi
金额：
$ 1.34万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Atherosclerosis involves deposits of excessive cholesterol and its esters mainly in the vascular system. On the cellular level, this excessive deposition is result of receptor-regulated uptake of oxidized forms of low-density lipoproteins. It may be possible to correct this situation by introducing into the circulation an alternate lipid carrier that woudd not be receptor directed and that would distribute lipids wore evenly. The objective of this study, therefore, is to investigate the potential use of sulfated cyclodextrins as artificial carriers for atherogenic lipids in a non-receptor mediated manner. The results obtained were as hollows.1. Sulfoalkylated cyclodextrins enhanced the aqueous solubility of cholesterol and its esters though inclusion complexation, while sulfated cyclodextrins, which have the electric charges located near the cavity, were less effective.2. Electrophoretic and gel permeation chromatographic studies revealed that the sulfated cyclodextrins showed a selective reactivity toward chyromicron and very-low-density lipoprotein fractions, leading to their aggregation to macroparticles.3. The intravenous administration of the sulfated cyclodextrins was well tolerated in rats without conspicuous changes in blood chemistry values. Furthermore, the in-vitro hemolytic activity and local tissue irritancy of the sulfated cyclodextrins were much less than those of the parent and their hydrophilic derivatives.4. Repeated intravenous administration of the sulfated cyclodextrins to hereditary hyperlipidemic rabbits led to a gradual increase in total cholesterol in circulation and eventually to a relief of atherosclerotic lesions in the thoracic aorta.The intravenous administration of the sulfated cyclodextrins may be used in catalysis of distribution of lipids in organisms and in invasive procedures such as angioplasty, when lipids debris may be released into the blood stream.

动脉粥样硬化涉及过量胆固醇及其酯主要在血管系统中的沉积。在细胞水平上，这种过度沉积是低密度脂蛋白的氧化形式的受体调节摄取的结果。通过在循环系统中引入一种非受体导向的脂质载体来纠正这种情况是可能的，这种脂质载体可以使脂质分布均匀。因此，本研究的目的是研究硫酸化环糊精作为人工载体以非受体介导的方式用于致动脉粥样硬化脂质的潜在用途。所得结果为空心.磺烷基化环糊精通过包合作用提高了胆固醇及其酯的水溶性，而电荷位于空腔附近的硫酸化环糊精则作用不明显.电泳和凝胶渗透色谱研究表明，硫酸化环糊精对乳糜微粒和极低密度脂蛋白组分表现出选择性反应，导致它们聚集成大颗粒.硫酸化环糊精静脉给药在大鼠中耐受性良好，血液化学值无明显变化。此外，硫酸化环糊精的体外溶血活性和局部组织刺激性远低于母体及其亲水性衍生物.对遗传性高脂血症家兔反复静脉注射硫酸化环糊精可导致循环中总胆固醇逐渐增加，并最终减轻胸主动脉粥样硬化病变，静脉注射硫酸化环糊精可用于催化脂质在生物体中的分布，也可用于侵入性手术，如血管成形术，此时脂质碎片可能释放到血流中。