OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.
OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS:Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.
Authors: Ankur Singh; Rachit Agarwal; Carlos A Diaz-Ruiz; Nick J Willett; Peiyi Wang; L Andrew Lee; Qian Wang; Robert E Guldberg; Andrés J García Journal: Adv Healthc Mater Date: 2014-03-31 Impact factor: 9.933