PEG-free pH-Responsive Thermogels Containing Amphiphilic Polycationic Polyethylenimine Copolymers

Thermogels are a class of supramolecular hydrogels that exhibit reversible sol–gel phase transitions upon temperature changes and whose unique properties are critically dependent on their constituent polymers' hydrophilic–hydrophobic balance. To date, the overwhelming majority of thermogelling polymers employ poly(ethylene glycol) (PEG) as the archetypical hydrophilic segment, with the usage of other hydrophilic polymers such as polyethylenimine (PEI) virtually unknown. Herein, we expand the possibilities in thermogel polymer design through a family of PEG-free amphiphilic polymers comprising only PEI and poly(propylene glycol) (PPG) as the sole hydrophilic and hydrophobic segments, respectively, that can spontaneously self-assemble into micelles and supramolecular gel matrices. By leveraging well-established amine chemistry, we demonstrate easy and mild postsynthetic modification of these PEI-PPG copolymers by quaternarization with benzyl groups, allowing a convenient means to modulate the resulting thermogel properties. In addition, through systematic variation of the copolymers' hydrophobic–hydrophilic balance, we show that the critical gelation concentrations, gelation temperatures, and gel viscoelastic properties can be tuned. Finally, on top of temperature responsiveness, the PEI segment also afforded pH-responsiveness by protonating the basic amine groups under acidic conditions, offering additional opportunities for altering thermogel viscoelasticity through ph adjustment. The convenience of postsynthetic functionalization, new material properties, and dual stimuli-responsiveness of these polycationic PEI-PPG thermogels can potentially offer a vast material design space for many unique applications.