Folic Acid-Functionalized Chitosan-Coated Oleosomes Engineered for Enhanced Anti-Arthritic Delivery of Syzygium cumini Seed Extract

Background/Objectives: This study evaluated the therapeutic efficacy of folic acid-functionalized chitosan-coated oleosomes (F-CS-OL) loaded with Syzygium cumini (SYG) seed extract against rheumatoid arthritis (RA) in a complete Freund’s adjuvant (CFA)-induced arthritis rat model. Methods: Rats received treatments via the oral route for 11 days following arthritis induction. The colloidal formulation exhibited an average particle size of 80.78 ± 1.02 nm, a zeta potential of −15.5 ± 1.12 mV, and an encapsulation efficiency (EE) of 94.98 ± 0.56%, alongside characterization by TEM, FTIR, and DSC. CFA-induced arthritis produced a pronounced inflammatory and angiogenic response, marked by significantly elevated serum levels of TNF-α, IL-6, CRP, VEGF, ICAM-1, MMP-3, and CXCL13 compared with the normal control group. Results: While treatment with free SYG extract resulted in moderate reductions in these biomarkers, the nanoencapsulated extract (SYG-loaded F-CS-OL) produced significantly greater reductions in inflammatory, chemotactic, matrix-remodeling, and angiogenesis-associated biomarkers compared with the untreated CFA-induced arthritis group. Histopathological examination of joint tissues further supported the biochemical findings. Conclusions: Overall, SYG-loaded F-CS-OL exhibited potent anti-inflammatory, immunomodulatory activities and significantly reduced biomarkers associated with angiogenic signaling in CFA-induced arthritis in CFA-induced arthritis. These findings suggest that folic acid-functionalized nanocarriers may represent a promising strategy for enhancing the therapeutic potential of SYG; however, further pharmacokinetic and safety studies are warranted to support clinical translation.