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

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-01-29 DOI:10.1016/j.nano.2024.102735
Ningrong Chen PhD , Xin Wei PhD , Gang Zhao PhD , Zhenshan Jia PhD , Xin Fu PhD , Haochen Jiang BS , Xiaoke Xu BSc , Zhifeng Zhao PhD , Purva Singh PhD , Samantha Lessard BA , Miguel Otero PhD , Mary B. Goldring PhD , Steven R. Goldring MD , Dong Wang PhD
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Abstract

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.

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在小鼠骨关节炎模型中,单剂量热冲击性地塞米松原药可在 15 周内完全缓解关节疼痛
本研究旨在评估热致伸缩性聚合物地塞米松(Dex)原药(ProGel-Dex)在骨关节炎(OA)小鼠模型中的镇痛效果。在建立模型 12 周后,OA 小鼠接受 ProGel-Dex、剂量相当的 Dex 或生理盐水的单次关节内注射。与生理盐水和地塞米松对照组相比,ProGel-Dex能在15周的无行为能力测试中提供完全和持续的疼痛缓解。体内光学成像证实,在注射后的15周内,ProGel-Dex一直存在于关节中。根据显微 CT 分析,ProGel-Dex 治疗小鼠的软骨下骨厚度和内侧半月板骨量明显低于 Dex 和生理盐水对照组。除了体重增加的短暂延迟和终点肝脏和脾脏重量略微降低外,ProGel-Dex 治疗后没有观察到其他不良反应。这些研究结果表明,ProGel-Dex 有可能成为一种有效、安全的镇痛剂,用于治疗 OA 疼痛。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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