Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 00 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovského nám. 2, 162 00 Prague, Czech Republic.
Nanomedicine. 2024 Jan;55:102716. doi: 10.1016/j.nano.2023.102716. Epub 2023 Oct 30.
Rheumatoid arthritis is a chronic inflammatory autoimmune disease caused by alteration of the immune system. Current therapies have several limitations and the use of nanomedicines represents a promising strategy to overcome them. By employing a mouse model of adjuvant induced arthritis, we aimed to evaluate the biodistribution and therapeutic effects of glucocorticoid dexamethasone conjugated to a nanocarrier based on biocompatible N-(2-hydroxypropyl) methacrylamide copolymers. We observed an increased accumulation of dexamethasone polymer nanomedicines in the arthritic mouse paw using non-invasive fluorescent in vivo imaging and confirmed it by the analysis of tissue homogenates. The dexamethasone conjugate exhibited a dose-dependent healing effect on arthritis and an improved therapeutic outcome compared to free dexamethasone. Particularly, significant reduction of accumulation of RA mediator RANKL was observed. Overall, our data suggest that the conjugation of dexamethasone to a polymer nanocarrier by means of stimuli-sensitive spacer is suitable strategy for improving rheumatoid arthritis therapy.
类风湿性关节炎是一种由免疫系统改变引起的慢性炎症性自身免疫性疾病。目前的治疗方法存在一些局限性，而使用纳米药物代表了克服这些局限性的一种有前途的策略。通过使用佐剂诱导的关节炎小鼠模型，我们旨在评估基于生物相容的 N-(2-羟丙基)甲基丙烯酰胺共聚物的纳米载体连接的糖皮质激素地塞米松的体内分布和治疗效果。我们通过非侵入性荧光体内成像观察到地塞米松聚合物纳米药物在关节炎小鼠爪子中的积累增加，并通过组织匀浆分析进行了确认。地塞米松缀合物对关节炎具有剂量依赖性的愈合作用，与游离地塞米松相比，治疗效果得到了改善。特别是，观察到 RA 介质 RANKL 的积累明显减少。总体而言，我们的数据表明，通过刺激敏感间隔物将地塞米松与聚合物纳米载体偶联是改善类风湿性关节炎治疗的合适策略。
