Dual Stimuli-Responsive Redox-Active Injectable Gel by Polyion Complex Based Flower Micelles for Biomedical Applications

We developed and evaluated a redox-active injectable gel (RIG) comprising poly[4-(2,2,6,6-tetramethylpiperidine- N -oxyl)aminomethylstyrene]- b -poly(ethylene glycol)- b -poly[4-(2,2,6,6-tetramethylpiperidine- N -oxyl)aminomethylstyrene] (PMNT–PEG–PMNT) triblock copolymer and poly(acrylic acid) (PAAc). Cationic PMNT–PEG–PMNT and anionic PAAc formed polyion complexes (PIC) flower micelles without aggregation, which was confirmed by FRET analysis. We confirmed that the PIC flower micelles exhibited irreversible sol–gel phase transitions with increasing both temperatures and ionic strengths. The PIC flower micelles had a low viscosity at room temperature. The viscosity increased with increasing temperatures and ionic strengths, and the RIG was formed under physiological conditions. The RIG was able to provide sustained release of an anionic model drug for more than 4 weeks without an initial burst. These results indicated that the RIG has potential as an injectable system for pharmaceutical and biomedical applications such as a local delivery carrier for the controlled release of charged drugs such as proteins or siRNA.