National Institute of Pharmaceutical Education and Research - Ahmedabad, Opp. Airforce station, Gandhinagar, Gujarat, 382355, India.
Siemens Healthcare Pvt. Ltd, Hosur, Bangalore, Karnataka, 560100, India.
BMC Biotechnol. 2024 May 9;24(1):26. doi: 10.1186/s12896-024-00856-3.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.
The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s.
In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.
类风湿性关节炎（RA）是一种慢性炎症性自身免疫性疾病，会导致关节内炎症不可逆转。目前治疗 RA 的方法包括非甾体抗炎药（NSAIDs）、改善病情的抗风湿药（DMARDs）、皮质类固醇和生物制剂。为了克服传统疗法和经皮组织屏障相关的药物毒性，开发了一种可注射的载 NSAID 水凝胶系统，并对其疗效进行了探索。
水凝胶的表面形态和孔隙率表明它们模拟了天然细胞外基质，这对组织愈合非常有益。此外，将 NSAIDs（如双氯芬酸钠）载入水凝胶中，发现其体外药物释放模式为 24 小时内突释，随后可持续释放 50%药物，持续 10 天。DPPH 测定表明水凝胶具有良好的自由基清除活性。通过 MTT 测定进行的生物相容性研究证明了水凝胶具有良好的生物相容性，通过 RAW 264.7 细胞中的基因表达研究进行了水凝胶的抗炎活性研究，表明 COX-2、TNF-α 和 18s 等几个关键炎症基因的下调。
总之，拟议的细胞外基质模拟、温度敏感的原位水凝胶可用于关节内炎症调节，并可通过减少用药频率和在关节内提供最佳润滑来获益。
