Liposome-encapsulated methotrexate interactions with human chronic lymphocytic leukemia cells

The uptake of free and liposome-entrapped methotrexate (MTX) by human chronic lymphocytic leukemia cells was compared under incubation conditions resembling those encountered in vivo. Liposome encapsulation enhanced up to 200 times the association of MTX with these cells. Autoradiographic studies established an association of [3H]MTX liposomes with the cells. Such a mode of delivery did not significantly increase the amount of drug available to inhibit dihydrotolate dehydrogenase, which suggested that the liposome content was not readily available to the cytoplasmic sites of action. Increased doses of encapsulated MTX resulted in enzyme inhibitions that were similar to those obtained with the free drug. This finding demonstrates that higher doses of MTX delivered by liposomes could be potentially useful in overcoming drug-transport resistance.