Design and optimization of folate-targeted lipid-polymer hybrid nanoparticles co-encapsulating dexamethasone and curcumin for synergistic anti-inflammatory efficacy in rheumatoid arthritis

Background: Rheumatoid Arthritis (RA) is a chronic immune-mediated disorder characterized by synovial inflammation and joint destruction. Current therapies are limited by systemic toxicity and poor bioavailability. This research developed Dexamethasone (Dex) and Curcumin (Cur) loaded Folate Lipid Polymer Hybrid Nanoparticles (DCFLPs) to achieve synergistic anti-inflammatory action for RA. Methodology: DCFLPs were synthesized by the ionic gelation technique. Furthermore, Box-Behnken Design (BBD) formulations were optimized and evaluated for size distribution, PDI, ζ potential, structural features, % encapsulation efficiency (EE), in vitro release profile, and cell line studies using RAW 264.7 cells. Results and Discussion: Optimized DCFLPs revealed an average particle size of 287.8 ± 1.32 nm and PDI 0.25 with positive ζ potential 5.4 mV, and have shown high entrapment efficiencies for Dex (89.12 ± 0.087%) and Cur (98.27± 0.110%). Cytotoxicity assays showed superior anti-inflammatory activity, and enhanced cellular uptake was observed in cell line studies. Conclusion: DCFLPs offer an auspicious approach for targeted RA therapy by combining controlled drug release, reduced systemic toxicity, and enhanced site-specific delivery. These findings suggest that the synthesized formulation has the potential to serve as a viable approach for in vivo translation, future preclinical evaluation, and effective progression towards clinical application in RA management.