Characterizing, Understanding and Exploiting lipid-lipid interactions

表征、理解和利用脂质-脂质相互作用

• 批准号: 105958-2013
• 负责人: Lafleur, Michel
• 金额: $ 3.93万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=545226
• 关键词: Characterizing; Understanding; Exploiting; lipid; interactions

Lipids are amphiphilic molecules that play a pivotal role in several biological processes and possess a great potential for the fabrication of nanocarriers. Our research program aims at gaining a better understanding and control of the structures and functions of lipid self-assemblies, investigating 3 specific systems. First, some peptides and proteins can induce lipid efflux from cell membranes, a phenomenon that plays a critical role in sperm maturation and in cholesterol transport. Despite their prime importance, we lack an underlying molecular description of the mechanism of these lipid extractions. We will characterize peptide- or protein-induced lipid extraction of some key systems with an overall approach, from the lipid/protein-peptide association to the resulting mixed complexes. We will particularly examine the chemical and physical features dictating the extraction of specific lipids. Second, the lipids of the stratum corneum (the top layer of the epidermis) are largely responsible for skin impermeability, a property that is proposed to be linked to the unusual crystalline phase they form. We will examine the molecular origin of the formation of solid phases, characterizing the phase behavior of different model mixtures and determine the correlation between the crystalline phases and the impermeability of the SC lipid models. The resulting improved knowledge will contribute to maintaining a healthy skin barrier, and potentially to altering the barrier for transdermal drug delivery. Third, my group is developing a novel family of liposomes formed with a monoalkylated amphiphile and a sterol. These liposomes display some distinct properties including a very low permeability. We propose to push further the development of these novel nanovectors by creating non phospholipid liposomes with specific properties: e.g. stealth liposomes that have an interesting potential for intravenous drug delivery, liposomes with alkylated sugar group to create new nanocarriers with a potential for targeted drug delivery, and light-sensitive liposomes. We believe that the combination of the exceptional impermeability and controlled release response grants an interesting potential for these non phospholipid cholesterol-rich liposomes.

脂质是两亲性分子，在多种生物过程中发挥着关键作用，并且在纳米载体的制造方面具有巨大的潜力。我们的研究计划旨在更好地理解和控制脂质自组装的结构和功能，研究了 3 个特定系统。首先，一些肽和蛋白质可以诱导脂质从细胞膜流出，这种现象在精子成熟和胆固醇运输中发挥着关键作用。尽管它们非常重要，但我们缺乏对这些脂质提取机制的潜在分子描述。我们将通过整体方法来表征肽或蛋白质诱导的一些关键系统的脂质提取，从脂质/蛋白质-肽关联到所得混合复合物。我们将特别检查决定特定脂质提取的化学和物理特征。其次，角质层（表皮的顶层）的脂质在很大程度上导致了皮肤的不渗透性，这种特性被认为与它们形成的不寻常的结晶相有关。我们将研究固相形成的分子起源，表征不同模型混合物的相行为，并确定结晶相与 SC 脂质模型的不渗透性之间的相关性。由此产生的知识的改进将有助于维持健康的皮肤屏障，并有可能改变透皮药物输送的屏障。第三，我的小组正在开发一种由单烷基化两亲物和甾醇形成的新型脂质体家族。这些脂质体表现出一些独特的特性，包括非常低的渗透性。我们建议通过创建具有特定特性的非磷脂脂质体来进一步推动这些新型纳米载体的开发：例如，具有静脉药物递送潜力的隐形脂质体、具有烷基化糖基团的脂质体（可创建具有靶向药物递送潜力的新型纳米载体）以及光敏脂质体。我们相信，卓越的不渗透性和控释响应的结合为这些富含非磷脂胆固醇的脂质体赋予了有趣的潜力。