Design and synthesis of novel pH and temperature sensitive copolymers for injectable delivery

We have developed methods to synthesize a family of novel self-assembling, pH and temperature sensitive water-soluble multiblock copolymers based on poly(ethylene oxide) (PEO) and poly(diethylaminoethylmethacrylate) (PDEAEM) with a variety of nanoarchitectures.. We have developed oxyanionic polymerization techniques to synthesize di-, tri-, and pentablock copolymers of PEO, poly(propylene oxide) (PPO) and PDEAEM, and also random copolymers of poly(ethylene glycol) methyl ether methacrylate and PDEAEM. The pentablock copolymers self-assemble to form nanometer scale micelles in aqueous solutions and above a critical gelation temperature, the micelles entangle and self-assemble to form macroscale thermoreversible water-soluble physical gels. Aqueous solutions of these polymers at room temperatures can be injected into the body where they form physical gels for controlled delivery that eventually dissolve and release the entrapped molecules. They also possess the ability to undergo swelling/syneresis in response to changes in pH. These polymers were characterized by a number of techniques such as NMR, gel permeation chromatography, infrared spectroscopy, etc. Such smart injectable systems could be very useful for insulin in response to glucose changes. These cationic polymers also exhibit complexation with DNA at physiological pH values and are potential as gene therapy vectors.