Synthesis and Evaluation of Thermoresponsive PLA-PEG-PLA and pH/Temperature-Sensitive OS-PLA-PEG-PLA-OS Hydrogels as Injectable Drug Delivery Application

A series of pH/temperature-sensitive OS-PLA-PEG-PLA-OS copolymers that could create in situ hydrogels are synthesized by combining thermoresponsive PLA-PEG-PLA (poly lactide-poly ethylene glycol-poly lactide) with OS (oligoester serine—a pH-sensitive component). The characteristic features of the copolymers were systematically evaluated by analyzing the chemical structure, morphology, sol–gel transition, and in vitro degradation. Thanking to sulfonamide groups of OS blocks with excellent pH-sensitive property, the pentablock copolymers (OS-PLA-PEG-PLA-OS) possessed better stability related to pH and nature in buffer solution than those of the triblock copolymers (PLA-PEG-PLA). It is also found that the OS-PLA₁₉₆₀-PEG₁₇₅₀-PLA₁₉₆₀-OS hydrogel only exhibited the thermoresponsive behavior due to too long hydrophobic block in its structure, whereas, the OS-PLA₁₇₅₀-PEG₁₇₅₀-PLA₁₇₅₀-OS hydrogel (30 wt%) demonstrated dual pH/temperature-sensitive properties with superior characteristics including a safe gel range under pH ranging from 6.0 to 7.8 at the temperature of 37 °C and slow degradation rate. We believe that the present pH/temperature-sensitive hydrogel has a potential application as an injectable carrier for prolonged release of drugs.