INVIVO DISTRIBUTION OF LIPOSOMES BETWEEN PARENCHYMAL AND NON PARENCHYMAL-CELLS IN RAT-LIVER

Abstract

The in vivo uptake of [the antineoplastic agent] 3H-methotrexate containing 14C-cholesterol labeled liposomes was determined for the 2 major liver cell populations, parenchymal cells (PC) and nonparenchymal cells (NPC), after i.v. injection of the liposomes into normal rats, and rats with a portocaval shunt; this was followed by isolation and purification of the 2 cell types. At 1 h after injection, the purified NPC had bound 2-3 times more of the liposome-attached radioactivity per cell than the purified PC, but 6 h after injection the ratio was inverted. In animals with a portocaval shunt, the PC contained already 3-4 times more liposomal radioactivity per cell than NPC, 1 h after injection; however, the total uptake by the whole liver was not diminished under these conditions. Recalculating the data obtained from the isolated cells for the whole liver, 1 h after injection, the liver NPC had bound the same amount of liposomal radioactivity as liver PC, but this accounted for only 7% of the liver volume. After 6 h, the PC had bound 5 times more liposomal radioactivity than the NPC; this ratio is achieved already in animals with a portocaval shunt, 1 h after injection. This shift is simultaneously caused by a gain of PC-bound radioactivity, and a decrease of NPC-bound radioactivity.