Engineering and Optimization of Biogenic Silver Nanoparticles: A Multimodal Approach to Glucocorticoid-Based Rheumatoid Arthritis Management

The primary purpose of the present work was to formulate folic acid (FA) conjugated biogenic sliver nanoparticles (AgNPs) loaded with dexamethasone sodium phosphate (DSP) for the management of rheumatoid arthritis (RA). DSP is the potent glucocorticoids (GCs) which reduce the inflammatory cytokines but its application is restricted due to its unfavourable pharmacokinetics and significant adverse effects. Biogenic AgNPs were prepared from Piper nigrum (Pn@AgNPs) with chitosan as a stabilizing agent and loaded with DSP (DSP-Pn@AgNPs). DSP-Pn@AgNPs was optimized using response surface methodology, which was further modified with FA (FA-DSP-Pn@AgNPs). The conjugation of FA with DSP-Pn@AgNPs was verified by ¹H-NMR. FTIR and EDX analyses identified certain functional groups and quantified the presence of silver ions in the nanoconstructs, respectively. The XRD pattern of FA-DSP-Pn@AgNPs revealed its crystalline structure, whereas its spherical shape has been confirmed via images of SEM and TEM. The in vitro release of DSP from FA-DSP-Pn@AgNPs showed 94% release at pH 6.5 within 48 h, through Korsmeyer-Peppas kinetic model. FA-DSP-Pn@AgNPs show antioxidant capacity by inhabiting DPPH, H₂O₂, OH, and NO radicals, along with anti-inflammatory properties such as anti-proteinase, lipoxygenase, collagenase, and elastase. The study also found no significant cytotoxic effect on non-LPS-stimulated RAW 264.7 macrophages, confirming systemic drug toxicity reduction. On the other hand, it significantly reduces LPS-stimulated cell line implying a probable anti-inflammatory action in RA. Thus, this study presents a synergistic action to guide the rational design of multifunctional anti-RA nanoconstructs, which show promise for clinical use.