Dexamethasone palmitate encapsulated in palmitic acid modified human serum albumin nanoparticles for the treatment of rheumatoid arthritis.

Highlights•The DXP-PSA NPs were able to actively target the pro-inflammatory macrophages and lower TNF-α concentrations.•DXP-PSA NPs could selectively aggregate at inflammatory sites and extend the drug circulation time, increasing the half-life and relative bioavailability of DXP.•The nano formulation of DXP prevents bone and cartilage damage in the advanced AIA rat model at a rather low dosage of DXP (0.2 mg/kg).AbstractRheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.