• cellular internalization;
  • isolated endothelial cells;
  • isolated hepatocytes;
  • isolated Kupffer cells;
  • liposomes;
  • liver perfusion

ABSTRACT—Aims/Background: The mechanism of interaction and the role played by the vesicle lipid composition for the selective association between liposomes and liver cells were studied, at the ultrastructural level, by investigating both in situ and in vitro the interaction between hepatocytes, Kupffer and endothelial liver cells with egg-phosphatidylcholine (eggPC) or eggPC/stearylamine (9:1; mol:mol) reverse-phase evaporation (REV) liposomes. Methods: Liver cells from rats, isolated by enzymatic perfusion and purified by differential centrifugation, were incubated, in a rotating bath at 37°C, with liposomes (2.5 mM final liposomal lipid concentration). Cell aliquots were withdrawn and processed for electron microscope observation at fixed time intervals. Parallel experiments were carried out by in situ liver perfusion with liposome suspensions. Results and Conclusions: Our first conclusions are: 1) lipidic composition affects the rate of liposomes uptake and internalization by hepatocytes; 2) liposome uptake by hepatocytes or Kupffer cells is likely an endocytic process; 3) endothelial cells internalize lipid vesicles as well; 4) liposome uptake was due to a phagocytic activity for all isolated liver cells, while in the in situ observation endothelial cells seem to use another mechanism (fusion); and 5) the rate of internalization is related to the viability of the treated cells. Experimental data seem to indicate that differential behaviour in the internalization of lipid vesicles exists among parenchymal, Kupffer and endothelial liver cells. These differences suggest that clearance of liposomes by these cells involves two mechanisms (i.e., endocytosis or fusion) with different rates of uptake and internalization that facilitate the design of carriers that can deliver drugs preferentially to a specific liver cell type.