Treatment of rat arthritides with clodronate-containing liposomes.

Large multilamellar liposomes containing dichloro-methylene-bisphosphonate (clodronate; Clo), a bisphosphonate that becomes toxic when intracellularly concentrated, were used to therapeutically target macrophages (Mo) in rats with established adjuvant arthritis (AA; i.v. on days 10, 11, 12) or antigen-induced arthritis (AIA; i.v. or i.a. on 3 h, days 1, 2).In established AA, i.v. injection of Clo-liposomes led to significant, long-lasting amelioration of clinical parameters, and to reduced destruction of the ankle joint even several weeks after termination of treatment. In the acute phase of established AIA, intravenous treatment induced transient clinical amelioration, but did not counteract joint destruction. La. treatment in AIA was ineffective.Systemic treatment with anti-Mo principles induces amelioration of both AA and AIA; the improvement appears more profound in AA, i.e., the model with a more systemic character. Preliminary data indicate that depletion of Mo occurs in the liver rather than in spl...