Temperature and Redox‐Responsive Hydrogels Based on Nitroxide Radicals and Oligoethyleneglycol Methacrylate

Abstract

A temperature and redox‐responsive polymer hydrogel is constructed by randomly incorporating 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐methacrylate (TEMPO) stable nitroxide radicals and oligoethyleneglycol methacrylate (OEGMA) groups in a polymer network. TEMPO can be reversibly oxidized into an oxoammonium cation (TEMPO+) providing the redox‐responsive properties while the lower critical solubility temperature (LCST) of OEGMA results in temperature‐responsive properties. Since a rather low amount of di(ethylene glycol) dimethacrylate (OEGMA2) is used to chemically crosslink the polymer network, the accordingly formed hydrogels obtained after swelling with water consist of microgel particles with entangled polymer chains that are not chemically crosslinked. By varying the amount of TEMPO in the polymer network, it is demonstrated that the radical form of TEMPO aggregates into hydrophobic domains acting as physical crosslinking nodes in the hydrogels and further increasing the cohesion between microgel particles. Increasing the temperature results in two opposite effects on the solubility of TEMPO and OEGMA units. The oxidation of TEMPO into TEMPO+ also results in a deep change in the hydrogel properties since TEMPO+ units are essentially hydrophilic and do not aggregate into physical crosslinking nodes.

Synthesis and characterization of hydrogels containing redox‐responsive 2,2,6,6‐tetramethylpiperidinyloxy methacrylate and thermoresponsive N‐isopropylacrylamide

“…Indeed, we have demonstrated in our previous reports that TEMPO (or TMPM before oxidation) units are essentially hydrophobic and aggregate into nanodomains. [25,26] Those hydrophobic interactions are leading to physical crosslinks summing up to the chemical crosslinks provided by the bifunctional DEGDA monomer.…”

“…The swelling factor values are smaller for the P(TEMPO + -s-NIPAM) hydrogels compared to the P(TEMPO-s-NIPAM) ones in agreement with our previous studies on P(TEMPO-s-OEGMA) and P(TEMPO + -s-OEGMA) hydrogels. [25,26] The temperature-dependent swelling profiles of the P(TEMPO-s-NIPAM) hydrogels with varying amounts of TEMPO units and X CL equal to 0.13 are illustrated in Figure 7. As temperature increases, swelling decreases until 80 C, when all gels totally collapsed.…”

“…[28] On the other hand, we have previously demonstrated that solubility of TEMPO units increases as temperature increases. [26] This effect would explain why a complete collapse of the P(TEMPO-s-NIPAM) hydrogels is not observed above the LCST of NIPAM units but rather a slow desolvation of the hydrogels as temperature increases (Figure 7).…”

“…Although, OEGMA is characterized by an LCST behavior, its cloud point is located at a too high temperature (above 60°C) to allow the hydrogel to be exploited for bio‐applications. [ 26 ] This prompted us to replace it by NIPAM, inspired by the work of Fu et al [ 27 ] Therefore, the present contribution aims at synthesizing poly(TEMPO‐ statistical ‐ N ‐isopropylacrylamide) (P[TEMPO ‐s‐ NIPAM]) copolymer networks and studying the effects of the redox and temperature stimuli on their mechanical and physicochemical properties.…”

Stereocomplexation of Poly(lactic acid) and Chemical Crosslinking of Ethylene Glycol Dimethacrylate (EGDMA) Double-Crosslinked Temperature/pH Dual Responsive Hydrogels

“…As a drug carrier with good biocompatibility and strong practicability, the hydrogel has been widely applied in the field of medicine delivery in recent years [ 3 , 4 ]. Stimulus-responsive hydrogels (SRHs), also known as “smart” hydrogels, are being actively studied [ 5 , 6 , 7 ], and are generally defined as hydrogels that can change their swelling properties in response to external stimuli such as pH [ 8 , 9 ], light [ 10 ], electricity [ 11 ], magnetism [ 12 ], temperature [ 13 , 14 ], and redox [ 15 ]. The study of stimuli-responsive hydrogels has further improved the targeted release of drug-loaded hydrogels and expanded the application of hydrogels.…”