title: Clearance and maximum removal rate of liposomes in normal and impaired liver of rat.
abstract: In the present study the author described a new method for analysis of the reticuloendothelial system (RES) function, using blood clearance of liposomes containing encapsulated phenolsulfonphthalein as a marker. Various types and doses of liposomes were intravenously administered to rats and the clearance of liposomes from blood was observed. Large liposomes were cleared from blood at a faster rate than small ones. Large liposomes composed of phosphatidylcholine and cholesterol were mainly phagocytized with Kupffer cells. The rate of disappearance of liposomes from blood was able to be calculated. With increments of administered doses there was an associated decrease of the disappearance rate, which corresponded to the Lineweaver-Burk plot in the enzymatic process, and it was possible to calculate the maximum removal rate and Michaelis constant. Disappearance rates decreased after prior administration of large liposomes and the inhibitory mode was competitive. Disappearance rates decreased after pretreatment with dextran sulfate and the inhibitory mode differed from the competitive. In partially hepatectomized and CCl4 intoxicated animals, disappearance rates also decreased. Liposomes are easily prepared and non-toxic. The clearance test of liposomes is possible to evaluate the role of the phagocytic function of the RES, chiefly Kupffer cells, in various experimental and clinical conditions.
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D006498:Hepatectomy; D007728:Kupffer Cells / Q000502:physiology; D008081:Liposomes; D008099:Liver / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000502:physiology*; D010316:Particle Size; D010587:Phagocytosis; D010637:Phenolsulfonphthalein; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003911:Dextrans; D008081:Liposomes; D016264:Dextran Sulfate; D010637:Phenolsulfonphthalein