Targeted delivery of liposomal dexamethasone phosphate to the spleen provides a persistent therapeutic effect in rat antigen-induced arthritis

Although long-term suppression of experimental arthritis has been reported for liposomal glucocorticoids, direct effects on subsequent flare-up reactions have not been investigated. The glucocorticoid dexamethasone phosphate (DXM-P) was encapsulated in large, non-PEGylated liposomes (DPPC/DPPG/Chol, 50/10/40 mol%, size: 295 (SD 15) nm) and its therapeutic efficacy was compared with free (non-liposomal) drug in rat antigen-induced arthritis (AIA). The specific aim was to assess the therapeutic persistence of an initial acute phase treatment with liposomal DXM-P on the induction of a subsequent flare-up reaction. Intravenous injection of liposomal DXM-P (1.25 mg/kg body weight) at 6, 24 and 48 h following arthritis induction completely suppressed joint swelling. The tight treatment schedule was chosen based on the rapid kinetics of arthritis development in this model (6 h: half-maximal swelling; 24–48 h peak arthritis). No rebound was seen until day …