GLYCOSYLATED PROTEOLIPOSOMES--A NEW DELIVERY VEHICLE

糖基化蛋白脂质体——一种新的运载工具

• 批准号: 3431903
• 负责人: ANTHONY W SCOTTO
• 金额: $ 5.41万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-15 至 1993-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3431903
• 关键词: cell age; drug delivery systems; drug design /synthesis /production; erythrocytes; genetic manipulation; glycosylation; hydropathy; laboratory rabbit; lipid bilayer membrane; liposomes; membrane proteins; peptides; surface property; technology /technique

The objective of this proposal is to examine the concept of the proteoliposome as an alternative to the liposome as a in vivo vehicle. The recent discovery of the spontaneous incorporation of integral membrane proteins into preformed unilamellar vesicles to form proteoliposomes allows, for the first time, the consideration of the proteoliposome as a feasible and economical alternative to the liposome for in vivo applications. The insertion of glycosylated integral membrane proteins derived from erythrocyte membranes, sialoglyco- and glyco-proteins, results in a stable modification of the surface of the vesicles potentially superior to that provided by the inclusion of glycolipids in liposomes; we hypothesize that the glycocalyx of these proteoliposomes can be "tailored" to result in a more persistent in vivo vehicle than that possible with a liposome composed of only lipids. It has already been shown that the proteoliposome is more stable in solution than similar liposomes; the initial aims of this study will be directed towards as examination of the relative stability of the proteoliposome versus the liposome with the components of blood. Subsequently, we will examine the intravascular persistence of various constructs of glycosylated proteoliposomes and determine whether the glycosylated proteoliposome can serve as a model for future drug delivery or hemoglobin carrier vehicles. The current aims are designed to test this concept in the most simple approach by using proteoliposomes prepared from erythrocyte integral membrane proteins derived from the same species as the recipient of the proteoliposome infusion (New Zealand rabbits), thereby avoiding most immunological complications. However, the long-term goal of this research is to construct an immunologically safe proteoliposome by synthesizing the simplest glycosylated hydrophobic (peptide) protein anchor required to provide a stable glycocalyx on the liposome by genetic engineering and/or organic synthesis.

本提案的目的是审查 蛋白脂质体作为脂质体的替代物作为体内媒介物。 最近发现的自发纳入积分 膜蛋白进入预先形成的单层囊泡， 蛋白脂质体允许，第一次，考虑 蛋白脂质体作为脂质体的可行且经济的替代物 用于体内应用。 插入糖基化整合 来自红细胞膜的膜蛋白，唾液酸糖基和 糖蛋白，结果在一个稳定的修饰的表面， 囊泡可能上级通过包含 脂质体中的糖脂;我们假设这些糖萼 蛋白脂质体可以被“定制”以导致更持久的体内代谢。 与仅由脂质组成的脂质体相比，载体是可能的。 它 已经证明脂蛋白体在溶液中更稳定 比类似的脂质体;本研究的最初目的将是指导 作为检查蛋白脂质体的相对稳定性 与脂质体和血液成分相比。 后续我们将 检查各种结构的血管内持久性， 糖基化的蛋白脂质体，并确定是否糖基化 蛋白脂质体可以作为未来药物递送的模型， 血红蛋白载体。 目前的目标旨在测试这一点 概念在最简单的方法通过使用蛋白脂质体制备 来自同一物种的红细胞膜整合蛋白 作为蛋白脂质体输注的接受者（新西兰兔）， 从而避免大多数免疫并发症。 但 这项研究的长期目标是构建一个免疫安全的 蛋白脂质体通过合成最简单的糖基化疏水 （肽）蛋白质锚需要提供一个稳定的糖萼上 通过基因工程和/或有机合成制备脂质体。