Liposome-incorporated dexamethasone palmitate inhibits in-vitro lymphocyte response to mitogen.

Abstract

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