In Vitro Evaluation of Thermosensitive PLGA–PEG–PLGA Hydrogels for Sustained Dexamethasone Delivery and Anti-Inflammatory Effects in Prostate Epithelial Cells

Background: Thermosensitive hydrogels have been widely investigated for localized drug delivery; however, their in vitro physicochemical stability, degradation behavior, and cell-level anti-inflammatory performance require systematic evaluation before further translational studies. In particular, prostate epithelial inflammation remains an underexplored application scenario for such delivery platforms. Methods: In this study, a PLGA–PEG–PLGA thermosensitive hydrogel was evaluated as a sustained delivery system for dexamethasone. The copolymer was characterized by GPC, FTIR, and ¹H NMR. Sol–gel transition behavior and viscoelastic properties were assessed using micro-DSC and rheological analysis. The microstructure of the drug-loaded hydrogel was examined by SEM. Degradation behavior was investigated under physiological (PBS, 37°C) and accelerated alkaline conditions. Cytocompatibility and anti-inflammatory effects were evaluated in RWPE-1 prostate epithelial cells. Results: SEM revealed an interconnected porous network structure in the drug-loaded hydrogel. Degradation studies showed high structural stability in PBS with minimal mass loss over 14 days, while rapid degradation occurred under alkaline conditions, confirming hydrolytic degradability. The hydrogel enabled sustained dexamethasone release and maintained good cytocompatibility. Notably, dexamethasone-loaded hydrogels significantly reduced IL-6 and IL-8 secretion, whereas blank hydrogels showed no intrinsic anti-inflammatory effect. Conclusion: This work provides a comprehensive in vitro evaluation of a thermosensitive PLGA–PEG–PLGA hydrogel for sustained dexamethasone delivery at the cellular level. The results clarify the relationship between hydrogel microstructure, degradation behavior, and diffusion-dominated drug release, establishing a solid foundation for future in vivo investigations.