Career Program: Molecular Design of Surface Modified Vesicles and Liposomes: A Theoretical Study

职业计划：表面修饰囊泡和脂质体的分子设计：理论研究

• 批准号: 9624268
• 负责人: Igal Szleifer
• 金额: $ 28.5万
• 依托单位: Purdue Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-15 至 2001-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9624268&HistoricalAwards=false
• 关键词: Career; Program; Molecular; Design; Surface

9624268 Szleifer Vesicles and liposomes are aggregates formed by spherically closed bilayers of amphiphilic molecules. The ability of the lipsome to dissolve large quantities of molecules in their core and its solubility in aqueous environments makes them ideal systems for drug delivery. In recent years it was found that grafting polymers to the surface of the liposomes increases the longevity of these aggregates in the blood stream. Furthermore, by chemically modifying the grafted polymer free end-group with molecules that have large affinities to specific cell receptors, the liposomes can be used for targeted delivery. Despite the importance of polymer-modified liposomes as premier drug carriers, there is no systematic understanding of the factors that govern their stability, longevity, and ability to target specific cells. A systematic theoretical study of the behavior of liposomes and vesicles modified by grafted polymer chairs will be performed. The single-chain mean-field theory will be used to study the behavior of the chain molecules (surfactants and polymers) that comprise the aggregates. This approach provides accurate conformational and thermodynamic information as compared with experimental measurements. The aim of the work is to systematically study the conditions under which modified aggregates can achieve longevity, thermodynamic stability and specific targeting. The work consists of finding the compositions of surfactants ( or lipids), cholesterol and polymer that will form stable vesicles within a range of size that is optimal for drug delivery. The ability of the grafted chains to prevent protein adsorption on the surface of the vesicles will be studied. Specific polymer chains that combine the ability to prevent protein adsorption with conformational properties that enhance targeting of the carrier to specific cells. The microscopic understanding of the behavior of polymer modified vesicles that will be achieved should able the development of new types of ag gregates for use as reagents that can be used in separation processes, such as protein separation and solubilization of small hydrophobic molecules in aqueous media. Theoretical studies will be carried out in close collaboration with three experimental groups that are investigating: 1) the use of end-functionalized polymer-modified liposomes for targeted drug delivery, 2) vesicle-membrane fusion induced by chemical modification of the vesicle and 3) protein adsorption on polymer-modified surfaces. The teaching plan is divided into two parts. One describes the approach to be taken in formal classroom teaching. The other presents the different projects that go beyond the formal teaching requirements. In the former, the basic idea is to provide the students with the links between physical processes, mathematical tools and experimental measurements. Understanding this relationship enables students to quickly grasp new concepts based on previously learned subjects. The informal activities that will be undertaken include special topic discussions, lectures and research for undergraduate students interested in specific applications of the general field of physical chemistry. These activities will be confined to select small groups of students; the aim being to provide the personalized attention that is not generally available in large formal classes. Furthermore, the teaching plan also includes special topic research projects for undergraduate and graduate students. ***

9624268 szleifer囊泡和脂质体是由两亲分子的球形封闭双层形成的聚集体。 Lipsome在其核心中溶解大量分子的能力及其在水性环境中的溶解度使它们成为药物输送的理想系统。 近年来发现，将聚合物接枝到脂质体表面会增加血液中这些聚集体的寿命。 此外，通过化学修饰接枝聚合物的无端组，具有对特定细胞受体具有较大亲和力的分子，可以将脂质体用于靶向递送。 尽管聚合物修饰的脂质体是主要药物载体的重要性，但对控制其稳定性，寿命和靶向特定细胞的能力的因素没有系统的了解。 将对通过移植聚合物椅子修饰的脂质体和囊泡的行为进行系统的理论研究。 单链平均场理论将用于研究构成聚集体的链分子（表面活性剂和聚合物）的行为。 与实验测量相比，这种方法提供了准确的构象和热力学信息。 这项工作的目的是系统地研究修饰的聚集体可以实现寿命，热力学稳定性和特定靶向的条件。 该作品包括找到表面活性剂（或脂质），胆固醇和聚合物的组成，这些组合物将在最佳的药物输送范围内形成稳定的囊泡。 将研究接枝链防止囊泡表面蛋白质吸附的能力。 特定的聚合物链结合了防止蛋白质吸附的能力与构象性能，从而增强载体对特定细胞的靶向。 如果能够开发可用于分离过程中的新型Ag Gregates，那么对聚合物改性囊泡的行为的显着理解，例如蛋白质分离和水溶液中小疏水分子的溶解。 理论研究将与正在研究的三个实验组密切合作：1）使用最终官能化聚合物修饰的脂质体用于靶向药物递送，2）囊泡膜膜融合，囊泡的化学修饰和3）蛋白质在聚合物改性表面上吸附。 教学计划分为两个部分。 一个人描述了在正规课堂教学中要采取的方法。 其他提出了超出正式教学要求的不同项目。 在前者中，基本思想是为学生提供物理过程，数学工具和实验测量之间的联系。 了解这种关系使学生可以根据以前学科的主题快速掌握新概念。 将要进行的非正式活动包括针对对物理化学一般领域的特定应用感兴趣的本科生的特殊主题讨论，讲座和研究。 这些活动将仅限于选择一小群学生；目的是提供大型正式课程中通常不可用的个性化注意力。 此外，教学计划还包括针对本科生和研究生的特殊主题研究项目。 ***