A SINGLE INTRAARTICULAR INJECTION OF LIPOSOMALLY CONJUGATED METHOTREXATE SUPPRESSES JOINT INFLAMMATION IN RAT ANTIGEN-INDUCED ARTHRITIS

In this study, we sought to determine whether liposomal preparations c ontaining a phospholipid conjugate of methotrexate and dimyristoylphos phatidylethanolamine (MTX-gamma-DMPE) incorporated within their lipid membranes are effective in suppressing established joint inflammation in a monoarticular model of arthritis in the rat. Arthritis was induce d in the right knee joint of Lewis rats. The rats were treated with a single intra-articular injection of either free methotrexate (MTX), li posomal MTX [MTX-multilamellar vesicles (MLV)-1.2 mu m or MTX-small un ilamellar vesicles (SUV)-100 nm], control liposomes (E-LIPO) or saline into the inflamed knee 7 days after arthritis induction. There was no significant difference in knee swelling in MTX-, saline- and E-LIPO-t reated rats up to 21 days after treatment. However, MTX-MLV treatment produced a significant reduction in knee swelling (26.5 +/- 6.0%; mean +/- S.E.M.) 1 day after intra-articular injection compared with MTX ( 3.5 +/- 3.5%) and MTX-SUV (14.4 +/- 2.4%), respectively. Over the next 20 days, knee swelling in MTX-MLV-treated rats fell progressively and almost returned to normal. MTX-MLV treatment also inhibited the cellu lar infiltration associated with the arthritis. Large multilamellar li posomal preparations of MTX-gamma-DMPE are more effective than free MT X and MTX-SUV in suppressing inflammation. Their differential effects in treating the antigen-induced arthritis model are related to their r etention within the joint space.