IS CONTROL OF DISTRIBUTION OF LIPOSOMES BETWEEN TUMORS AND BONE-MARROW POSSIBLE

The objective of this study is to clarify to what extent the accumulat ion of liposomes from the blood into the tumor and bone marrow can be controlled by liposome size and membrane fluidity. Liposomes with diff erent diameters (50-400 nm) and different membrane fluidity were prepa red from hydrogenated egg phosphatidylcholine (HEPC) or egg phosphatid ylcholine (EPC), cholesterol (Ch) and dicetylphosphate in various mola r ratios, These liposomes were injected intravenously into rats bearin g Yoshida sarcoma, and the ratios of the accumulation of liposomes in the tumor to those in the bone marrow, liver and spleen were compared. The tumor-to-bone marrow accumulation ratio increased with the decrea se in liposome size from 400 to 50 nm, This ratio was greater than tho se for the liver and spleen at all sizes. Although tumor-to-liver accu mulation ratios of 50- and 100-nm HEPC-containing liposomes were highe r than those of EPC-containing liposomes, no obvious difference in tum or-to-bone marrow or tumor-to-spleen accumulation ratios was found bet ween these liposomes, Tumor-to-bone marrow accumulation ratio of HEPC- containing liposomes increased remarkably with the decrease in Ch cont ent from 40 to 30 or 20 mol% compared with ratios for the liver and sp leen. Interestingly, the tumor uptake clearance of liposomes of the sa me size was constant regardless of their membrane fluidity. These find ings show that the increases in these accumulation ratios are due to t heir decreased uptake clearance by the bone marrow. Furthermore, the u ptake of 50-nm HEPC-containing liposomes by the bone marrow was specif ically inhibited by preinjection of other liposomes, but not when they were exposed in advance to in vivo components. These observations sug gest the involvement of in vivo component(s) in the uptake of these li posomes by the bone marrow. We conclude that small HEPC-liposomes with low Ch content show their significantly decreased uptake by the bone marrow due to their decreased recognition by this tissue.