On the mechanism of hepatic transendothelial passage of large liposomes.
Liposomes of 400 nm in diameter can cross the 100-nm fenestrations in the endothelium of the hepatic sinusoid, provided they contain phosphatidylserine (PS) but not phosphatidylglycerol (PG) [Daemen et al. (1997) Hepatology 26, 416]. We present evidence indicating that (i) the PS effect does not involve a pharmacological action of this lipid on the size of the fenestrations, (ii) fluid-type but not solid-type PS liposomes have access to the hepatocytes and (iii) the lack of uptake of PG liposomes by hepatocytes is not due to a lack of affinity of the hepatocytes for PG surfaces. We conclude that the mechanism responsible for the uptake of large PS-containing liposomes by hepatocytes in vivo involves a mechanical deformation of these liposomes during their passage across the endothelial fenestrations.
Romero
E L
EL
Groningen University Institute for Drug Exploration, Faculty of Medical Sciences, Department of Physiological Chemistry, University of Groningen, The Netherlands.
Morilla
M J
MJ
Regts
J
J
Koning
G A
GA
Scherphof
G L
GL
D000818:Animals; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010715:Phosphatidylglycerols / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D051381:Rats
D008081:Liposomes; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines