Polyacetals: Water-Soluble, pH-Degradable Polymers with Remarkable Thermoresponsive Behavior

Columbia University, New York NY

Investigators

Abstract

NON-TECHNICAL SUMMARY: The fundamental nature of polymer applications has changed markedly over the years. While early applications called for polymers that were strong and light, resistant to chemicals and environmentally inert, today's applications demand smart polymers that can shrink, expand, thicken, or change effectively their material properties in response to a host of different external stimuli. Thermally responsive polymers exhibit a drastic and discontinuous change in some physical property, usually solubility, with change in temperature. The proposed research focuses on the development of an exciting new family of thermoresponsive polyacetal polymers with remarkable properties that are well suited to a myriad of biomedical and other applications. The new polyacetals are the first water-soluble thermoresponsive polymers to be intrinsically biodegradable. Their thermal transitions can be predicted from their molecular structure and tuned to high precision anywhere within a range of about 6-80°C, they are biocompatible, and they degrade under acidic conditions to form neutral degradation products that do not cause inflammation inside the body. The new polyacetal materials have the potential to be used in a broad range of technologies that are important not only economically, but that affect the quality of life, in particular those relating to medicine. An example of such an outcome might be development of polyacetals as potential drug delivery vehicles for the treatment of pancreatic cancer. Personnel development is an important outcome of the proposed research, and involves training and mentoring of a postdoctoral researcher for a position in academia, involving Master's students enrolled in an innovative new program that provides undergraduate science majors the opportunity to obtain a Master's degree in engineering, and developing the research skills of an undergraduate student. The personnel involved with this research will also gain important insight into critical biomedical problems through collaborations with practicing medical clinicians. TECHNICAL SUMMARY: The main technical research objectives are to develop the polyacetal materials as a new family of temperature-responsive, pH degradable polymers; and to explore the fundamental origins of their remarkable lower critical solution temperature (LCST) behavior, scaling linearly with the number of carbon and oxygen atoms in the polymer repeat units. LCST phase diagrams will be modeled to extract the concentration and temperature dependence of the interaction parameter and thereby explore the fundamental origin of the unique temperature response. The research plan also seeks to extend the number of polyacetals available to meet current and future needs for multi-stimuli-responsive polymers. Extensions include exploring several new types of monomers, developing monomers that provide main chain functionality to graft functional moieties of interest and preparing macromonomers with terminal azide and alkyne groups that can be coupled together by click chemistry. The macromonomers enable preparation of dual responsive gels and block copolymers that can be used in important applications ranging from smart drug delivery vehicles for cancer treatment that biodegrade in acidic tumors, to polymers for controlled release of pesticides that slowly degrade upon contact with soil. The research plan includes modeling the remarkable LCST behavior in order to understand its linear dependence on molecular structure, as well as correlating other important properties such as the block copolymer critical micelle concentration and pH-dependant degradation rates with the molecular structure. Successful modeling will provide the ability to predict thermal response and physical behavior so that the properties of these remarkable new polyacetal-based materials can be designed a priori to meet the needs of specific applications.