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

CTS-9973524 Santore，Maria MLehigh大学磷脂双层囊泡或脂质体是几十年来研究的焦点，它构成了细胞膜的基础，并且一直是生物技术和非生物应用的囊泡技术的核心。 人们通常认为，表面活性剂，如磷脂，提供了很大的可能性，化学变化，应该是囊泡壁的主要构件。 然而，提议的访问教授和后续研究计划的动机是最近发现某些共聚物，即使是基于商品材料如聚乙烯（PE）和聚环氧乙烷（PEO）的共聚物，也会形成类似于经典脂质体的囊泡或“多聚体”。 多聚体具有革新技术的潜力，如靶向递送、微反应器和微发酵器、传感器和致动器，甚至形成人工细胞的基础，因为它们可以拓宽双层膜可以存活的条件范围，并且它们增加了可以被工程化到膜中的性质的类型。有待开发和实施。 第一个探索是建立形成多核糖体的共聚物化学和结构的范围，以及这些膜对pH和化学扰动的鲁棒性。 在撰写本提案时，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化学物质也可能成功的策略。 下一个问题是什么范围内的基本膜性能可以实现（机械性能和横向扩散），以及如何将这些与磷脂囊泡比较。 由于多核糖体的最终性能将取决于其渗透性和功能化部分可以掺入膜中的程度，因此也将考虑多核糖体的问题。 最后，在许多受控递送应用和模拟细胞行为的情况下，多核糖体与其他多核糖体和外表面的粘附将是关键的。 拟议的计划包括在这一领域的试点研究，以形成工作的基础上超越了休假。POWRE的钱被要求支持一个休假的Santore教授花了一年在宾夕法尼亚大学的Hammer教授的实验室，在那里多聚核糖体首次发现。 该实验室设备齐全，可用于制作和研究基本的囊泡粘附研究。 在休假期间，Santore将学习制造和操纵囊泡的基本技术，这些知识是在利哈伊无法获得的。 工作将做对的问题，其中共聚物形成多聚体和机械，扩散和渗透性能的多聚体膜。 此外，在访问教授期间，将开始研究囊泡粘附和将专门分子掺入多核糖体壁的问题。 从这最后两个子课题的结果将形成未来的计划在利哈伊，超越访问教授，以及未来的合作锤和桑托之间的基础。 申请的资金包括Santore教授休假期间的工资，以及休假后在Lehigh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

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