ROS-Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

A reactive oxygen species (ROS)-sensitive degradable polymer would be a promising material in designing a disease-responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) (PEG–PCL–PEG or EG₁₂–CL₂₀–EG₁₂) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0−37.0 wt%. In particular, the aqueous PEG–PCL–PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0–37.0 wt%, whereas the aqueous PEG–PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG–PCL–PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle-based thermogel of PEG–PCL–PEG with ROS-triggering degradability is a promising injectable material for biomedical applications.