Cationic, Anionic, and Amphoteric Dual pH/Temperature-Responsive Degradable Microgels via Self-Assembly of Functionalized Oligomeric Precursor Polymers

Multiresponsive smart materials with the capacity to reversibly change properties (i.e., size, charge) upon the application of more than one stimulus (i.e., temperature, pH) offer potential in numerous biotechnology and biomedical applications. However, their typical lack of degradability limits their potential in vivo use. Herein, we demonstrate the use of an aqueous thermally driven self-assembly approach based on hydrazide- and aldehyde-functionalized poly­(N-isopropylacrylamide) (PNIPAM) oligomers functionalized with pH-ionizable cationic or anionic comonomers for fabricating degradable temperature/pH dual-responsive microgels. The self-assembled microgels show properties analogous to conventional cationic or anionic PNIPAM microgels, retaining their thermal responsiveness while exhibiting pH-driven swelling upon functional comonomer ionization. Amphoteric microgels can also be produced by mixing cationic- and anionic-functionalized precursor polymers during the self-assembly process that reproduce the high-pH/low-pH parabolic swelling response observed in conventional amphoteric microgels. Coupling the precise dual-responsive swelling responses achievable with the degradability of the hydrazone cross-links, self-assembled charged PNIPAM microgels offer potential for improved performance in drug delivery applications requiring dual pH/temperature-specific delivery (e.g. infection sites or cancer).