LIPOSOME-INCORPORATED DEXAMETHASONE PALMITATE INHIBITS IN-VITRO LYMPHOCYTE-RESPONSE TO MITOGEN

The use of liposomes for the pulmonary delivery of corticosteroid is a n area that is under active We have recently developed a novel liposom al corticosteroid preparation based on the incorporation of dexamethas one palmitate (DMP) within the bilayer of small unilamellar vesicles ( SUVs) made of egg yolk phosphatidylcholine (EPC) and cholesterol; mola r ratio EPCC:cholesterol: DMP, 4:3:0.3. In the present study, the biol ogical activity of DMP-SUVs was evaluated using the lymphocyte transfo rmation test with peripheral blood mononuclear cells (PBMCs) and a gam ma-interferon production assay. Results showed that DMP-SUVs (but not empty SUVs) inhibited [H-3]thymidine uptake and gamma-interferon produ ction by concanavalin A-stimulated PBMCs by 94 and 96%, respectively, at a concentration corresponding to 10(-6) M dexamethasone. The inhibi tion by DMP-SUVs was found to require a 24-h pre-incubation with unsti mulated PBMCs. suggesting that interaction of SUVs with lymphocytes ma y be altered by mitogen stimulation. We conclude that our DMP liposoma l preparation is biologically active and may be considered a promising alternative to conventional local glucocorticoid therapy.