Rabbits with a bilateral
antigen-induced
arthritis were injected intra-articularly in one joint with
methotrexate as the free
drug or entrapped in
liposomes. Free
methotrexate (1 mg) injected as a single dose at the time of
antigen challenge, suppressed the development of joint swelling and the rise in skin surface temperature of treated joints by 20-30% compared with contralateral control arthritic joints. The beneficial effect of
methotrexate occurred within 24 h of injection and was maintained for at least 56 days. However,
methotrexate was ineffective in suppressing
arthritis when injected 7 days after
antigen challenge. Liposomal
methotrexate suppressed the development of
arthritis at a dose one-tenth that of the free
drug and it was also effective in suppressing
arthritis of 7 days duration, although significant beneficial effects of liposomal
methotrexate were delayed for 10 to 14 days after injection. Neither free nor liposomal
methotrexate was effective in suppressing an established
arthritis, having no significant effect on joint swelling or skin surface temperature when injected 21 and 35 days after
antigen challenge. At the end of the study, 8 or 9 weeks after induction of
arthritis, the joints were examined morphologically and histologically. Free
methotrexate generally had no significant effect on joint pathology. However, liposomal
methotrexate suppressed the development of synovial
hyperplasia, cellular infiltration and the erosion of cartilage and bone when injected at the time of
antigen challenge or 7 days later, but affected none of these parameters in an established
arthritis of 3 weeks duration.