Liposomes Kupffer cells

Dijkstra J, van Galen WJ, Scherphof GL. Effects of ammonium chloride and chloroquine on endocytic uptake of liposomes by Kupffer cells in vitro. Biochim Biophys Acta 1983 804(l) 58-67. 

Keywords. Gontrast agents, Triiodobenzenes, Liposomes, Metal chelates, Hepatocytes, Kupffer cells... 

The following chapter reviews tissue-specific X-ray contrast agents, in particular liver-specific substances. Although many different approaches including hepatocyte and Kupffer-cell targeting utilizing iodinated compounds have been followed, no small molecule could be obtained that is effective and safe. Two different approaches, however, do seem to be feasible and will be followed in the future. These are extracellular iodinated X-ray contrast agents encapsulated into liposomes and liver-specific lanthanide chelates. 

Conventional liposomes and lipid complexes. Liposomes were used initially as a model system for cellular membranes to study the biochemistry of membrane proteins.85 Consequently, when liposomes were first tried as a drug delivery system, their bilayers were composed of un-derivatized naturally occurring lipids. Most of such conventional liposomes are taken up by the MPS phagocytes within a few hours of injection, mostly by liver Kupffer cells and spleen macrophages.9 Inside the endosomes and lysosomes of those cells, liposomes are degraded. If the liposomal drugs are membrane permeable, they then can diffuse from the endosomal compartments to the cytoplasm of the macrophage cells and slowly reenter the blood circulation. Because such a clearance... 

Biodistribution of liposomes is a very important parameter from the clinical point of view. Liposomes can alter both the tissue distribution and the rate of clearance of the drug by making the drug take on the pharmacokinetic characteristics of the carrier (10, 11). The pharmacokinetic variables of the liposomes depend on the physiochemical characteristics of the liposomes, such as size, surface charge, membrane lipid packing, steric stabilization, dose, and route of administration. As with other microparticulate delivery systems, conventional liposomes are vulnerable to elimination from systemic circulation by the cells of the reticuloendothelial system (RES) (12). The primary sites of accumulation of conventional liposomes are the tumor, liver, and spleen compared with non-liposomal formulations (13). Many studies have shown that within the first 15-30 min after intravenous administration of liposomes between 50 and 80% of the dose is adsorbed by the cells of the RES, primarily by the Kupffer cells of the liver (14-16). 

Key words Liposomes, Macrophages, Clodronate, Depletion of macrophages, Kupffer cells. 

After intravenous administration, liposomes are rapidly removed from blood, primarily by cells of the RES, and, foremost, by the liver (Kupffer cells). The half-lives of... 

Roerdink, F., Dijkstra, J., Hartman, G., Bolscher, B., and Scher-phof, G. L. (1981). The involvement of parenchymal, Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes, Biochim. Biophys. Acta, 677, 79-89. 

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