Biocompatible Thermoresponsive Hydroxypropyl Cellulose-Based Hydrogel Microspheres with Temperature-Controllable Drug Release and Lubricating Property

Temperature-responsive hydrogels are ideal intelligent carriers for drug delivery due to their ability to enable precise and on-demand drug release. Compared to synthetic polymers with similar thermoresponsive properties, hydroxypropyl cellulose (HPC) offers distinct advantages for drug delivery applications due to its wider availability from natural sources, lower cost, and superior biocompatibility and biodegradability. However, the lower critical solution temperature (LCST) is relatively high (40–50 °C), and it cannot form a cross-linked network by itself, which limits its practical application in drug delivery. Herein, we innovatively developed an injectable, thermoresponsive, drug-loaded hydrogel microsphere (HPC-AGE/PVA@DS). This system achieves on-demand drug release via thermoresponsive hydrogel shrinkage at a physiological temperature (37 °C). Poly(vinyl alcohol) (PVA) effectively prevents microsphere fracture during shrinkage, thereby avoiding burst drug release. The microspheres also exhibit excellent lubricity, along with outstanding biocompatibility and superior anti-inflammatory efficacy compared to nonthermosensitive hydrogels. This stimuli-responsive localized drug delivery system offers a promising platform for treating osteoarthritis (OA) and other chronic diseases.