**6. Conclusion**

Multifactorial pathogenesis is the hallmark in RA causing bone fragility and functional erosion linked disability in extreme conditions. Although, conventional therapeutic formulations alone or in combination may relieve the symptoms, these are associated with complex adverse reactions. Dose-escalation, immunogenicity, systemic toxicity, and non-specific biodistribution in tissues warrant SDDS development. Stimuli-responsive NPs target specific inflammatory intermediaries, thereby suppressing the pathophysiological cascade, that may alleviate RA symptoms and delay joint destruction. Therefore, both the approaches may be exploited for achieving dose reduction coupled with drug accumulation at the targeted inflamed joint.

#### **Acknowledgements**

LB is thankful to UGC, and VS is thankful to ICMR, Govt of India for Senior Research Fellowship. VK is thankful to Individual Fellowship from European Union's Research and Innovation program, Marie Skłodowska-Curie grant agreement No. 890507.
