DIFFERENTIAL-EFFECTS OF METHOTREXATE AND LIPOSOMALLY CONJUGATED METHOTREXATE IN RAT ADJUVANT-INDUCED ARTHRITIS

In this study we evaluated the comparative efficacy of free and liposo mally conjugated methotrexate on both disease induction and suppressio n of acute inflammation in rat adjuvant-induced arthritis. Rats were g iven either empty liposomes (E-LIPO), free methotrexate (MTX) or the l iposomally conjugated methotrexate (MTX-LIPO) at a dose of 100 mu g/da y for 7 consecutive days by the intravenous route. When MTX treatment was initiated on the day of arthritis induction the drug suppressed bu t did not abolish the development of joint inflammation. Free MTX had no significant anti-inflammatory effect upon an established arthritis when dosing was commenced on day 11 post-adjuvant induction. Conversel y, MTX-LIPO did not affect the progression of the arthritis when dosin g was started on day 0, but exerted a significant anti-inflammatory ef fect on an established arthritis. MTX-LIPO treatment was significantly less haematotoxic than free MTX.