Center for Materials Synthetic Biology, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Department of Bone and Joint Surgery & Guangxi Key Laboratory of Regenerative Medicine, International Joint Laboratory on Regeneration of Bone and Soft Tissue, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Mol Pharm. 2024 Jan 1;21(1):87-101. doi: 10.1021/acs.molpharmaceut.3c00462. Epub 2023 Dec 15.
Osteoarthritis (OA) affects numerous patients worldwide, and there are no approved disease-modifying drugs. Repurposing FDA-approved small molecular drugs could be a promising alternative strategy to treat OA. Disulfiram (DSF), a clinically approved drug for treatment of alcoholism, inhibits inflammasome activation and exhibits a protective role in interleukin-1β-induced cardiac injury. However, its efficacy in treating OA remains to be explored due to its poor water solubility and stability, which limit its use in OA treatment. Here, the anti-inflammatory effect of DSF is evaluated in vitro, and a double-layer encapsulation approach is developed for intra-articular delivery of DSF for OA treatment . DSF is loaded into poly(lactic--glycolic acid)-based nanoparticles and encapsulated in gelatin methacrylate microgels through a microfluidic device. Results show that DSF effectively inhibits the expression of key inflammatory cytokines in OA chondrocytes, and the double-layer encapsulation approach reduces the burst release of DSF and prolongs its retention time in the study. Sustained release of DSF from microgels mitigates cartilage inflammation and subchondral bone erosion in a monoiodoacetate-induced rat OA model. This work demonstrates the potential of repurposing FDA-approved drugs for OA treatment and provides a promising platform for intra-articular delivery of small molecules for superior therapeutic effect.
骨关节炎（OA）影响全球众多患者，目前尚无批准的疾病修饰药物。重新利用美国食品和药物管理局批准的小分子药物可能是治疗 OA 的一种有前途的替代策略。双硫仑（DSF）是一种临床批准用于治疗酗酒的药物，可抑制炎症小体激活，并在白细胞介素-1β诱导的心脏损伤中发挥保护作用。然而，由于其较差的水溶性和稳定性，限制了其在 OA 治疗中的应用，其在治疗 OA 中的疗效仍有待探索。在此，评估了 DSF 的体外抗炎作用，并开发了一种双层包封方法，用于关节内递送 DSF 治疗 OA。将 DSF 装载到聚（乳酸-乙醇酸）基纳米粒子中，并通过微流控装置将其包封在明胶甲基丙烯酸酯微凝胶中。结果表明，DSF 可有效抑制 OA 软骨细胞中关键炎症细胞因子的表达，双层包封方法可减少 DSF 的爆发释放并延长其在研究中的保留时间。微凝胶中 DSF 的持续释放可减轻单碘乙酸诱导的大鼠 OA 模型中的软骨炎症和软骨下骨侵蚀。这项工作证明了重新利用美国食品和药物管理局批准的药物治疗 OA 的潜力，并为小分子的关节内递药提供了一个有前途的平台，以实现更好的治疗效果。
