Targeted delivery to joints of the rheumatoid arthritis drug betulin using folic acid-coated nanoparticles based on human serum albumin

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovitis, cartilage and bone damage, and potential permanent disability. The conventional pharmacotherapies for rheumatoid arthritis, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, predominantly confer symptomatic palliation. Betulin, a pentacyclic triterpene derived from birch bark, has shown promise in treating RA. But it suffers from poor solubility, low oral bioavailability, short circulation time, and potential adverse effects. This study aimed to enhance the therapeutic efficacy and targeted delivery of betulin to arthritic joints by encapsulating it in folic acid-coated human serum albumin nanoparticles (FA-BT@NPs). The FA-BT@NPs system demonstrated significant improvements in drug delivery, achieving higher betulin concentrations in the joints of rats with collagen-induced arthritis compared to free betulin. This targeted approach resulted in enhanced therapeutic efficacy and reduced systemic side effects, highlighting the potential of FA-BT@NPs as a precise drug delivery system for RA. The drug delivery system represents a promising strategy for the targeted treatment of rheumatoid arthritis, offering improved drug delivery to affected joints while minimizing off-target effects. This approach could provide pre-clinical evidence for more effective and safer therapies for rheumatoid arthritis.