Synthesis and thermoresponsive behaviors of biodegradable Pluronic analogs

Pluronic analogs based on block copolymers of poly(propylene oxide) and poly(ethyl ethylene phosphate) (PEEP‐PPO‐PEEP) were synthesized, and the thermoresponsive behavior, including aggregation at low concentration and gelation at high concentration were studied. At lower concentrations up to 10 wt %, thermo‐induced aggregation of PEEP‐PPO‐PEEP was demonstrated by UV‐vis absorbance measurements using 1,6‐diphenyl‐1,3,5‐hexatriene as a probe. Microthermal analyzes showed symmetrically endothermic and exothermic thermograms during the thermo‐induced aggregation and de‐association processes, which was also associated with the dehydration and rehydration of PPO blocks, as revealed by the variable temperature NMR measurements. Thermo‐induced aggregation with the increased temperatures was also observed by dynamic light scattering. At higher concentration from 20 to 40 wt %, the aqueous solution of PEEP‐PPO‐PEEP underwent thermo‐induced phase transitions from a clear solution to a turbid solution, then to opaque gel and syneresis phases, depending on the molecular weights of PEEP blocks. Such a thermoresponsive hydrogel was used for doxorubicin incorporation. Sustained release of drug was achieved from the gel, demonstrating the polyphosphoester‐based Pluronic analogs' potential for biomedical applications.