Pharmacokinetics, Tissue Distribution and Metabolism of Intravenously Administered Digalactosyldiacylglycerol and Monogalactosyldiacylglycerol in the Rat

AbstractA bilayer forming galactolipid, digalactosyldiacylglycerol (DGalDG) has been identified as a tool with suitable physicochemichal properties for pharmaceutical formulation work. One possible application is as a carrier for liposome entrapped drugs for intravenous administration. The fate of intravenously administered galactolipids is not known. In this study liposomal dispersions of galactolipids, containing [3H]fatty acid labelled DGalDG or monogalactosyldiacylglycerol (MGalDG) were injected intravenously in the rat and the disappearance from blood and uptake by tissues were examined. The T1/2 of [3H]DGalDG in plasma was 3 to 5 minutes. Of the tissues examined (liver, spleen, kidneys, lung, heart, stomach, upper and lower small intestine and colon), the liver contained the highest radioactivity per g tissue after both 15 min. and 4 h. Autoradiographic examinations after 15 min, 1 h and 4 h showed that the uptake of radiolabeled DGalDG and MGalDG occurred mainly to the hepatocytes. Less than 6 % of...

[1]  M. Bergqvist,et al.  Isolation and purification of digalactosyldiacylglycerols , 1995 .

[2]  T. V. van Berkel,et al.  Ligand size is a major determinant of high-affinity binding of fucose- and galactose-exposing (lipo)proteins by the hepatic fucose receptor. , 1994, The Biochemical journal.

[3]  T. V. van Berkel,et al.  Characterization of the interaction of galactose-exposing particles with rat Kupffer cells. , 1994, The Biochemical journal.

[4]  Malcolm N. Jones.  Carbohydrate-mediated liposomal targeting and drug delivery , 1994 .

[5]  H. Akerlund,et al.  Isolation of pigment-free bulk lipids from thylakoids. , 1993, Biochimica et biophysica acta.

[6]  E. Ingley,et al.  Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60. , 1991, Blood.

[7]  P. Andreasen,et al.  Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells. , 1990, Cell regulation.

[8]  A. Nanci,et al.  Routine use of backscattered electron imaging to visualize cytochemical and autoradiographic reactions in semi-thin plastic sections. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  T. Baker,et al.  Drug delivery using vesicles targeted to the hepatic asialoglycoprotein receptor. , 1987, Biochimica et biophysica acta.

[10]  S. G. Sprague.  Structural and functional consequences of galactolipids on thylakoid membrane organization , 1987, Journal of bioenergetics and biomembranes.

[11]  M. Yamazaki,et al.  Induction of macrophage growth by lipids. , 1986, Journal of immunology.

[12]  A. Nilsson,et al.  A role for hepatic lipase in chylomicron and high density lipoprotein phospholipid metabolism. , 1984, Journal of lipid research.

[13]  A. Nilsson,et al.  Metabolism of chylomicron phosphatidylethanolamine in the rat. , 1984, Biochimica et biophysica acta.

[14]  G. Scherphof,et al.  Targeting of lactosylceramide-containing liposomes to hepatocytes in vivo. , 1983, Biochimica et biophysica acta.

[15]  Y. Rahman,et al.  Differential uptake of liposomes varying in size and lipid composition by parenchymal and kupffer cells of mouse liver. , 1982, Life sciences.

[16]  R. Scow,et al.  Hydrolysis of chylomicron phosphatidylcholine in vitro by lipoprotein lipase, phospholipase A2 and phospholipase C. , 1976, Biochimica et biophysica acta.

[17]  C. Litchfield.  Analysis of Triglycerides , 1972 .

[18]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.