POWRE: Polysomes: Biologically-Inspired Vesicles of Block Copolymers for Targeted Delivery and Controlled Release Applications

POWRE：多聚体：用于靶向递送和控释应用的嵌段共聚物的生物启发囊泡

• 批准号: 9973524
• 负责人: Maria Santore
• 金额: $ 10万
• 依托单位: Lehigh University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9973524&HistoricalAwards=false
• 关键词: POWRE; Polysomes; Biologically; Inspired; Vesicles

CTS-9973524Santore, Maria MLehigh UniversityPhospholipid bilayer vesicles, or liposomes, a focus of research for several decades, form the basis for cellular membranes and have been at the core of vesicle technology for biotechnological and non-bio applications alike. It has generally been assumed that surfactants like phospholipids, which offer large possibilities for chemical variations, should be the primary building blocks for vesicle walls. The proposed Visiting Professorship and follow-up research program was, however, motivated by the extremely recent discovery that certain copolymers, even those based on commodity materials such as polyethylene (PE) and polyethylene oxide (PEO), form vesicles or "polysomes" that appear similar to classical liposomes. Polysomes have the potential to revolutionalize technologies such as targeted delivery, microreactors and microfermentors, sensors and actuators, and even form the basis of artificial cells because they can broaden the range of conditions where bilayer membranes can survive and they increase the types of properties that can be engineered into membranes.This proposal addresses a number of fundamental issues which must be resolved in order for polysome technology to be developed and implemented. The first quest is to establish the range of copolymer chemistries and architectures that form polysomes, and the robustness of these membranes to pH and perturbations in the chemistry. At the time this proposal was written, only one system was examined and shown to form vesicles. This work presents a strategy for anticipating other chemistries which may also succeed. The next issue is what range of basic membrane properties can be achieved (mechanical properties and lateral diffusivity) and how these compare with phospholipid vesicles. Since the ultimate performance of polysomes will depend on their permeability and the extent to which functionalized moieties can be incorporated into the membrane, the issues will also be considered with polysomes. Finally, in many controlled delivery applications and instances that mimic cell behavior, the adhesion of the polysome with other polysomes and external surfaces will be critical. The proposed program includes pilot studies in this area to form the basis of work beyond the sabbatical leave.POWRE monies are requested to support a sabbatical leave for Professor Santore to spend a year in Professor Hammer's lab at the University of Pennsylvania, where polysomes were first discovered. This laboratory is well-quipped for the fabrication and study of basic vesicle adhesion studies. During the sabbatical, Santore will learn the basic techniques for fabricating and manipulating vesicles, knowledge that could not be acquired at Lehigh. Work will be done towards the questions of which copolymers form polysomes and the mechanical, diffusional, and permeation properties of polysomes membranes. Also during the Visiting Professorship, work will be initiated to study the issues of vesicle adhesion and the incorporation of specialized molecules into the polysome wall. Results from these last tow subtopics will form the foundation for future programs at Lehigh, beyond the Visiting Professorship, and future collaborations between Hammer and Santore. Funds are requested for of Professor Santore's salary during the sabbatical, and basic equipment for vesicle studies at Lehigh beyond the sabbatical leave.Key Words: Materials; Membranes; Vesicle; POWRE; Biomedical; Surfactants

磷脂双层囊泡或脂质体是几十年来研究的焦点，是细胞膜的基础，也是生物技术和非生物应用囊泡技术的核心。一般认为，表面活性剂，如磷脂，提供了很大的化学变化的可能性，应该是囊泡壁的主要组成部分。然而，访问教授和后续研究计划的动机是最近发现某些共聚物，甚至是基于聚乙烯（PE）和聚氧聚乙烯（PEO）等商品材料的共聚物，形成囊泡或“聚体”，看起来与经典脂质体相似。聚体有可能彻底改变诸如靶向递送、微反应器和微发酵罐、传感器和致动器等技术，甚至可以形成人造细胞的基础，因为它们可以扩大双层膜生存的条件范围，并增加可以设计成膜的特性类型。这一建议解决了一些必须解决的基本问题，以便发展和实施多聚体技术。第一个任务是建立共聚物化学和结构的范围，形成多体，以及这些膜对pH值和化学扰动的稳健性。在撰写这一建议时，只有一个系统被检查并显示形成囊泡。这项工作提出了一种预测其他可能成功的化学反应的策略。下一个问题是可以实现的基本膜性能（机械性能和横向扩散率）的范围以及这些与磷脂囊泡的比较。由于聚体的最终性能将取决于它们的渗透性和功能化部分可以被纳入膜的程度，因此也将考虑聚体的问题。最后，在许多受控递送应用和模拟细胞行为的实例中，多聚体与其他多聚体和外表面的粘附将是至关重要的。拟议的方案包括这方面的试点研究，以形成休假后工作的基础。桑托尔教授在宾夕法尼亚大学哈默教授的实验室度过了一年的休假，在那里首次发现了多聚体。本实验室设备齐全，可进行基本囊泡黏附研究的制备和研究。在休假期间，桑托尔将学习制造和操纵囊泡的基本技术，这些知识在利哈伊大学是学不到的。工作将针对哪些共聚物形成多体以及多体膜的机械、扩散和渗透特性的问题进行。此外，在访问教授期间，将开始研究囊泡粘附和特殊分子进入多体壁的问题。最后两个子主题的结果将成为里海未来项目的基础，除了访问教授，以及哈默和桑托雷之间的未来合作。申请经费用于支付桑托尔教授在休假期间的工资，以及休假后在利哈伊进行囊泡研究的基本设备。关键词：材料；膜;囊泡;POWRE;生物医学;表面活性剂