British Journal of Rheumatology 1994;33:530-533 SUPPRESSION OF ADJUVANT-INDUCED ARTHRITIS BY LIPOSOMALLY CONJUGATED METHOTREXATE IN THE RAT

A phospholipid conjugate of methotrexate was synthesized and liposomally formulated in order to determine whether such a formulation could modulate the severity of experimentally induced arthritis in the rat. Lewis rats were immunized with Mycobacterium butyricum and after the onset of joint inflammation were treated intravenously with methotrexate liposomes (MTX-LIPO). This preparation was significantly better in reducing established joint inflammation than comparable doses of the free drug or empty liposomes of identical lipid composition. Haematopoietic toxicity associated with MTX-LIPO was significantly less than seen with comparable doses of the free drug. KEY WORDS: Liposome, Methotrexate, Adjuvant arthritis, Rat. ORAL methotrexate (MTX) provides an effective treat-ment of RA when given weekly in low doses, adverse events occur frequently but are generally mild in sever-ity and reversed by cessation of MTX therapy. Alter-native routes of administering MTX to patients with RA have included intra-articular injection but the results of these clinical studies were disappointing; lack of efficacy being attributed to the rapid clearance of th