Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis

• Published in: Nanomedicine Vol. 57; p. 102735
• Main Authors: Chen, Ningrong, Wei, Xin, Zhao, Gang, Jia, Zhenshan, Fu, Xin, Jiang, Haochen, Xu, Xiaoke, Zhao, Zhifeng, Singh, Purva, Lessard, Samantha, Otero, Miguel, Goldring, Mary B., Goldring, Steven R., Wang, Dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024
• Subjects: Dexamethasone; Osteoarthritis; Pain; Prodrug; Thermoresponsive hydrogel; Pain; Dexamethasone; Prodrug; Osteoarthritis; Thermoresponsive hydrogel
• ISSN: 1549-9634; 1549-9642; 1549-9642
• DOI: 10.1016/j.nano.2024.102735

In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain. A single intra-articular injection of the thermoresponsive polymeric dexamethasone prodrug nanomedicine (ProGel-Dex) into the mouse model of post-trauma osteoarthritis provides >15 weeks of complete pain relief without triggering significant adverse effects. [Display omitted]