Foong W C, Green K L
School of Pharmacy & Biomedical Sciences, University of Portsmouth, UK.
J Pharm Pharmacol. 1993 Mar;45(3):204-9. doi: 10.1111/j.2042-7158.1993.tb05533.x.
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.
将双侧抗原诱导性关节炎的兔子，在一个关节内注射游离药物甲氨蝶呤或包裹于脂质体中的甲氨蝶呤。在抗原激发时单次注射游离甲氨蝶呤（1毫克），与对侧对照关节炎关节相比，可使治疗关节的肿胀发展及皮肤表面温度升高受到20% - 30%的抑制。甲氨蝶呤的有益作用在注射后24小时内出现，并持续至少56天。然而，在抗原激发7天后注射甲氨蝶呤，对抑制关节炎无效。脂质体甲氨蝶呤以游离药物十分之一的剂量就能抑制关节炎的发展，并且对持续7天的关节炎也有效，尽管脂质体甲氨蝶呤的显著有益作用在注射后延迟10至14天出现。游离和脂质体甲氨蝶呤在抑制已形成的关节炎方面均无效，在抗原激发21天和35天后注射时，对关节肿胀或皮肤表面温度均无显著影响。在研究结束时，即关节炎诱导8或9周后，对关节进行形态学和组织学检查。游离甲氨蝶呤通常对关节病理无显著影响。然而，脂质体甲氨蝶呤在抗原激发时或7天后注射，可抑制滑膜增生、细胞浸润以及软骨和骨的侵蚀，但对持续3周的已形成关节炎的这些参数均无影响。
