Recent studies have demonstrated in vivo synergistic immunosuppressive and anti‐inflammatory capacity of dexamethasone (Dx) and naproxen (NAP) in collagen‐induced arthritis (CIA) rats. However, the molecular basis of this synergistic effect is barely understood. The low solubility of these drugs and their adverse effects hamper their efficacy on the treatment of inflammatory processes making nanoparticulated systems promising candidates to overcome these drawbacks. The aim of this work is the preparation of polymeric nanoparticles (NPs) that combine NAP and Dx in different concentrations, and the evaluation of the expression of key genes related to autoimmune diseases like CIA. To do so, self‐assembled polymeric NPs that incorporate covalently‐linked NAP and physically entrapped Dx are designed to have hydrodynamic properties that, according to bibliography, may improve retention and colocalization of both drugs at inflammation sites. The rapid uptake of NPs by macrophages is demonstrated using coumarine‐6‐loaded NPs. Dx is efficiently encapsulated and in vitro biological studies demonstrate that the Dx‐loaded NAP‐bearing NPs are noncytotoxic and reduce lipopolysaccharide‐induced NO released levels at any of the tested concentrations. Moreover, at the molecular level, a significant synergistic reduction of Il12b transcript gene expression when combining Dx and NAP is demonstrated.

中文翻译：

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结合地塞米松和萘普生对巨噬细胞中Il12b转录的协同抑制作用的聚合物纳米颗粒。

最近的研究表明，在胶原诱导的关节炎（CIA）大鼠中，地塞米松（Dx）和萘普生（NAP）的体内协同免疫抑制和抗炎能力。但是，这种协同作用的分子基础还很少被理解。这些药物的低溶解度及其不良影响妨碍了它们在炎性过程的治疗中的功效，从而使纳米颗粒系统有望克服这些缺点。这项工作的目的是制备以不同浓度结合NAP和Dx的聚合物纳米颗粒（NP），并评估与自身免疫性疾病（如CIA）相关的关键基因的表达。为此，结合了共价连接的NAP和物理包裹的Dx的自组装聚合物NP被设计为具有流体动力学特性，根据参考书目，可能会改善两种药物在炎症部位的保留和共定位。载有香豆碱-6的NP证明了巨噬细胞对NP的快速吸收。Dx被有效地包裹起来，并且体外生物学研究表明，在任何测试浓度下，Dx负载NAP的NPs均无细胞毒性，并降低了脂多糖诱导的NO释放水平。此外，在分子水平上，Dx被有效地包裹起来，并且体外生物学研究表明，在任何测试浓度下，Dx负载NAP的NPs均无细胞毒性，并降低了脂多糖诱导的NO释放水平。此外，在分子水平上，Dx被有效地包裹起来，并且体外生物学研究表明，在任何测试浓度下，Dx负载NAP的NPs均无细胞毒性，并降低了脂多糖诱导的NO释放水平。此外，在分子水平上，当结合Dx和NAP时，证实了II12b转录本基因表达。