Preparation of a platycodin D microsphere gel and evaluation of its therapeutic effects on osteoarthritis in rats.

Osteoarthritis (OA) is a leading cause of disability; however, current treatments are limited by systemic side effects and the need for frequent administration. Herein, a sustained intra-articular delivery system was developed by encapsulating Platycodin D (PD), a bioactive saponin derived from Platycodon grandiflorus, into PLGA microspheres and further integrating them with a thermosensitive hydrogel to enhance joint retention and therapeutic efficacy. In this study, a PD-loaded microsphere gel (PD-MS-gel) was constructed by combining optimized PD-loaded microspheres (PD-MS) with a thermosensitive gel, and the particle size, encapsulation efficiency (EE), and drug loading (DL) were systematically evaluated. The biocompatibility and reactive oxygen species (ROS) scavenging capability of PD-MS-gel were determined in C28/I2 chondrocytes, and its therapeutic performance was investigated in an OA rat model by assessing body weight, knee swelling, and histological changes. The optimized PD-MS exhibited a uniform spherical morphology with a mean particle size of 41.52 ± 1.46 µm, an EE of 76.55%, and a DL of 5.68%. PD-MS-gel achieved sustained drug release for more than 10 days, effectively reduced burst release, and displayed a sol-gel transition temperature of 34 °C. In vitro experiments demonstrated excellent cytocompatibility and enhanced ROS scavenging activity, while in vivo results confirmed that PD-MS-gel significantly alleviated OA symptoms, reduced joint swelling, and promoted cartilage repair. Collectively, this microsphere-hydrogel composite system integrates sustained release with prolonged joint retention, offering a promising materials-based strategy for intra-articular OA therapy.