Treatment of established collagen induced arthritis with prostaglandin E-1incorporated in lipid microspheres

Objective. In view of evidence obtained from in vitro and in vivo experimen ts that prostaglandin E-1 (PGE(1)) has regulatory effects on disordered imm une responses and inflammation, we investigated whether lipo-PGE(1), an eff icient drug delivery system incorporating PGE(1) into lipid microspheres, c an ameliorate arthritis in the collagen induced arthritis (CIA) model of rh eumatoid arthritis (RA). Methods. DBA/1J male mice were immunized with bovine type II collagen in ad juvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE(1) (5-50 mu g/kg) or lipid vehicle as a control . Arthritis was assessed over a 10 day treatment period by monitoring for p aw swelling and clinical score. Histopathology of the arthritic hind paws w as also evaluated. Lipo-PGE(1) accumulation in arthritic joint tissues was measured using H-3 labeled PGE(1) incorporated in lipid microspheres. Results. Arthritis was significantly suppressed in lipo-PGE(1), treated mic e compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respec tively) in a dose-dependent manner. Histopathological assessment showed a s ignificant reduction of pannus formation and joint destruction in lipo-PGE( 1) treated mice compared with controls (p < 0.05). Lipo-PGE(1) preferential ly accumulated in arthritic joints for a longer period than free PGE(1). Conclusion. Using an efficient drug delivery system, PGE(1) can suppress CI A, and lipo-PGE(1) may have a potential therapeutic role in RA.