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

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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