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Rheumatoid arthritis (RA) is a chronic autoimmune disease that requires anti-inflammatory drugs, analgesics, and tissue protectors. To deal with this disease, the pain and inflammation should be relieved in the first stage, and tissue protectors should be used to restore joint damage that limits movement. Therefore, a comprehensive multifunctional core–shell nanocomposite (TFH@TA/AuNPs-HDA) with a continuous anti-inflammatory effect and a special tissue protection potential in the core was designed. Here, the hydrothermal reaction was applied to synthesize the hydrogel core from tragacanth and frankincense gums; then, the shell was self-assembled with tannic acid/gold nanoparticles (TA/AuNPs) and 10-hydroxy-2-decanoic acid (10-HDA). The biocompatibility, anti-inflammatory properties, and tissue protective effect of TFH@TA/AuNPs-HDA were investigated on RAW264.7 cells and in collagen-induced RA rat models. Moreover, the molecular docking demonstrated the interactions of 10-HDA and AuNPs with NF-κB signaling pathway proteins, confirming the anti-inflammatory effect of 10-HDA and AuNP suppression of the NF-κB pathway. The results revealed that TFH@TA/AuNPs-HDA could be an appropriate system for RA therapy due to the synergistic alleviation of inflammation and joint tissue destruction.

Inflammation is the main complicating factor of chronic autoimmune diseases. Therefore, attenuating inflammation has a vital role in the treatment of these diseases. Biocompatibility and effective functions of ruthenium(III) complexes were previously confirmed, especially for cancer treatment. In the current study, a ruthenium(III) complex with deprotonated indigo ligands, Ru(HIndig) 3 , was synthesized and then loaded on the salep hydrogel (SAH) to obtain a natural anti-inflammatory nanocomposite (SAH-Ru(HIndig) 3 ). The SAH-Ru(HIndig) 3 nanocomposite was entirely characterized by spectroscopy methods, electron microscopy, elemental analysis, and thermogravimetry. The mean size of semispherical particles of SAH-Ru(HIndig) 3 was found to be about 184 ± 65 nm. The in vitro behaviors, including swelling capacity, degradation rate, free radical scavenging capability, and release profile of SAH-Ru(HIndig) 3 , were also evaluated. In addition, the biocompatibility and the effect of the nanocomposite on cell migration were examined in RAW264.7 cells. Furthermore, the anti-inflammatory effect of the nanocomposite against the cellular model of inflammation was investigated by determining inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10 mRNA levels. Consequently, the results revealed that SAH-Ru(HIndig) 3 effectively ameliorates inflammation and potentially affects cell migration. Hence, SAH-Ru(HIndig) 3 could be used to treat inflammatory autoimmune diseases.

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