Pharmacokinetic behavior of [57Co]Bleomycin liposomes in mice: comparison with the unencapsulated substance

The distribution and excretion of [Co]Bleomycin, dissolved in saline or encapsulated in liposomes, was studied in normal or tumor-bearing [P388 leukemia, reticulum cell sarcoma (RS)] mice. The free substance is cleared relatively quickly from the organism both after intravenous and intraperitoneal administration (t1/2 0.17 and 2.41 h, respectively), and is excreted predominantly via the urinary tract. In contrast, following entrapment in small unilamellar vesicles (SUV) or multilamellar vesicles (MLV), the Co radioactivity remains 7− to 30-fold longer in the blood stream and is detectable in considerable amounts in liver, spleen, lung and tumor of the RS model even after 48 h. Concomitantly, the renal excretion is diminished to about 50% of the free drug and the feces excretion is slightly increased, possibly due to the higher concentrations in the liver. Whereas the renal levels of radioactivity were similar with alt application forms of [Co]Bleomycin, there were marked differences in all the other tissues studied. After administration of SUV there was a higher activity in liver, brain and tumor, whereas MLV were more concentrated in spleen and lung. Therapeutic experiments confirmed the favorable results obtained with liposomes. While the free Bleomycin in the P388 leukemia had only a moderate influence on the lifetime of the animals with a treated/control value of 111%, encapsulation of the drug in SUV or MLV improved the results to 194 and 167%, respectively. In the intramuscular transplanted RS model, the SUV in a day 1 schedule had the same effect on tumor growth as the free drug in a day 1–4 schedule. These favorable results obtained with Bleomycin-containing liposomes make this drug formulation attractive for clinical use.