Synthesis and characterization of folate functionalized core-shell pluronic/chitosan nanoparticles against rheumatoid arthritis.

Significant advances in novel drug delivery systems have led to the development of ligand-conjugated nanoparticles, enabling targeted delivery of therapeutic agents to disease-specific sites. A widely adopted approach for treating rheumatoid arthritis involves targeting folate receptors, which are overexpressed in inflamed tissues. This study focused on formulating methotrexate-loaded, folate-conjugated core-shell polymeric nanoparticles (PF/CS). These nanoparticles were synthesized using self-micellization and ionic gelation techniques, resulting in particles with an average size of 185.0 ± 2.08 nm, a PDI of <0.5, and a zeta potential of 19.9 ± 2.23 mV indicating excellent stability and uniformity. Ligand conjugation was confirmed using 1H Nuclear Magnetic Resonance Spectroscopy and Fourier Transformed Infrared Spectroscopy. Further physicochemical characterization, including Differential Scanning Calorimetry, Thermo-Gravimetric Analysis, and X-ray Diffraction analysis, demonstrated good compatibility and thermal stability. In vitro studies showed sustained drug release for up to 72 h and higher cytotoxicity against RAW 264.7 macrophage cells with folate-conjugated PF/CS nanoparticles compared to non-conjugated ones. Ex-vivo hemocompatibility testing confirmed their non-hemolytic nature. Acute toxicity studies indicated biocompatibility and safety. In vivo assessments in rats showed enhanced therapeutic effects with folate-conjugated nanoparticles. In silico modeling supported experimental findings. It is concluded that folate-conjugated PF/CS nanoparticles offer a promising platform for sustained methotrexate delivery in rheumatoid arthritis treatment.