Design of tunable hyaluronic acid and O′-carboxymethyl chitosan formulations for the minimally invasive delivery of multifunctional therapies targeting rheumatoid arthritis

IF 10.7 1区 化学 Q1 CHEMISTRY, APPLIED Carbohydrate Polymers Pub Date : 2024-11-17 DOI:10.1016/j.carbpol.2024.123018
Daniel Fernández-Villa , Aitor Herraiz , Kyra de Wit , Fernando Herranz , María Rosa Aguilar , Luis Rojo
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Abstract

The development of injectable, dual-component formulations based on natural-based polysaccharides is a promising strategy for the localized treatment of rheumatoid arthritis (RA). In the present study, biomimetic formulations consisting of aldehyde-functionalized hyaluronic acid (AHA) and O-carboxymethyl chitosan (OCC) were developed, presenting rapid in situ gelation rates and finely tunable physicochemical properties. These two properties allowed for the controlled delivery of anti-inflammatory, antioxidant, and pro-regenerative agents (i.e., strontium-methotrexate (SrMTX) and europium-tannic acid nanocomplexes (EuTA NCs), making them suitable for application in in vivo RA-models. Biological analyses demonstrated the system's cytocompatibility and its ability to modulate the activity of human articular chondrocytes at the secretome level and scavenge nitric oxide (NO). Moreover, the loaded cargoes not only extended the anti-inflammatory properties of the formulation but also the radiolabeling of EuTA NCs with 68Ga allowed the visualization of the gel by positron emission tomography (PET). Overall, this work presents the design and in vitro evaluation of an easily modulable polymeric system that allows the in situ release of a multifunctional therapy with promising perspectives for RA treatment.
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设计可调透明质酸和 O′-羧甲基壳聚糖制剂,用于微创递送针对类风湿性关节炎的多功能疗法
开发基于天然多糖的可注射双组分制剂是局部治疗类风湿性关节炎(RA)的一种很有前景的策略。本研究开发了由醛功能化透明质酸(AHA)和O-羧甲基壳聚糖(OCC)组成的生物仿生制剂,具有快速的原位凝胶速率和可微调的理化特性。这两种特性使得抗炎、抗氧化和促再生剂(即甲氨蝶呤锶(SrMTX)和铕-单宁酸纳米络合物(EuTA NCs))的可控递送成为可能,从而使它们适合应用于体内 RA 模型。生物学分析表明了该系统的细胞相容性及其在分泌组水平调节人体关节软骨细胞活性和清除一氧化氮(NO)的能力。此外,负载的货物不仅扩展了制剂的抗炎特性,而且用 68Ga 对 EuTA NCs 进行放射性标记后,可通过正电子发射断层扫描(PET)观察凝胶。总之,这项工作展示了一种易于调节的聚合物系统的设计和体外评估,该系统允许原位释放多功能疗法,具有治疗 RA 的广阔前景。
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来源期刊
Carbohydrate Polymers
Carbohydrate Polymers 化学-高分子科学
CiteScore
22.40
自引率
8.00%
发文量
1286
审稿时长
47 days
期刊介绍: Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience. The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.
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