Immune response mediated by liposome-associated protein antigens. IV. Modulation of antibody formation by vesicle-encapsulated methotrexate.

Large unilamellar reverse-phase evaporation vesicles (REV) were used as a heterobifunctional carrier for a pharmacologically active agent and a protein antigen. Methotrexate (MTX) was encapsulated in the hydrophilic compartment of liposomal REV with or without surface-conjugated bovine serum albumin (BSA) antigen. The administration of MTX encapsulated within BSA-coated vesicles (MTX.REV-BSA) could either enhance or depress the anti-BSA plaque-forming cell (PFC) response in mice. On the other hand, the administration of MTX entrapped in plain vesicles (MTX.REV) produced essentially a suppressive effect on the PFC response stimulated by the simultaneous injection of a separate antigen, e.g. vesicle-conjugated BSA (REV-BSA). This suppression of the antibody response occurred, whether MTX.REV was injected 1 day before, during, or 1 day after the immunization with an antigen. These results indicate that liposome-encapsulation of a very limited drug dose can modify the immunobiological effect of the drug which, when presented in its free form at the same dose, exerts no appreciable action on the engendered immune response. Thus, the modulation of the immune response by a liposome-encapsulated drug appears to be influenced by the drug dose can modify the immunobiological effect of the drug which, when presented in its free form.