Therapeutic activity and biodistribution of a nano-sized polymer-dexamethasone conjugate intended for the targeted treatment of rheumatoid arthritis

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2023-10-30 DOI:10.1016/j.nano.2023.102716

Daniela Rubanová M.Sc. et M.Sc. , Svitlana Skoroplyas M.Sc., Ph.D. , Alena Libánská M.Sc. , Eva Randárová M.Sc. Ph.D. , Josef Bryja B.Sc. , Michaela Chorvátová M.Sc. , Tomáš Etrych RNDr. Ph.D. DSc. , Lukáš Kubala M.Sc. Ph.D.

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Abstract

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.

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用于类风湿性关节炎靶向治疗的纳米聚合物-地塞米松偶联物的治疗活性和生物分布

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。目前的治疗方法有一些局限性，而纳米药物的使用代表了一种克服它们的有希望的策略。通过佐剂性关节炎小鼠模型，我们旨在评估糖皮质激素地塞米松与基于生物相容性N-(2-羟丙基)甲基丙烯酰胺共聚物的纳米载体缀合的生物分布和治疗效果。我们使用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患关节炎的小鼠爪子中积累增加，并通过组织匀浆分析证实了这一点。与游离地塞米松相比，地塞米松偶联物对关节炎表现出剂量依赖性的愈合效果，并改善了治疗结果。特别是，观察到RA介质RANKL的积累显著减少。总的来说，我们的数据表明，通过刺激敏感间隔剂将地塞米松偶联到聚合物纳米载体上是改善类风湿性关节炎治疗的合适策略。

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

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.