Uptake of Liposomes Containing Phosphatidylserine by Liver Cellsin Vivoand by Sinusoidal Liver Cells in Primary Culture:In Vivo–in VitroDifferences

Abstract

The interaction with liver cells of liposomes containing different mol fractions of phosphatidylserine was investigatedin vivoandin vitro.Increasing the amount of liposomal phosphatidylserine from 10 to 30 mol% leads to a faster blood disappearance of the liposomes. Within the liver, which is mainly responsible for this elimination, these liposomes are only taken up by the hepatocytes and Kupffer cells. By contrast, sinusoidal endothelial cells,in vitro,do bind and internalize liposomes containing ≥30% phosphatidylserine at least as actively as Kupffer cells. The uptake by endothelial and Kupffer cells is inhibited by poly(inosinic acid) and other anionic macromolecules, suggesting the involvement of scavenger receptors. The lack of liposome uptake by endothelial cells underin vivoconditions can be attributed to plasma effects since addition of various sera caused severe reduction ofin vitrouptake of liposomes.In vivothe phosphatidylserine head groups may be masked by plasma proteins adsorbed to the liposomal surface, thus preventing recognition by receptors, which are intrinsically able to recognize phosphatidylserine.