Flow cytofluorometric investigation of the uptake by hepatocytes and spleen cells of targeted and untargeted liposomes injected intravenously into mice.
Untargeted liposomes (composition: PC-PS-cholesterol) and targeted liposomes (composition: PC-PS-cholesterol-lactosylceramide) having encapsulated concentration-quenched carboxyfluorescein were injected intravenously into mice. 1 h after injection, the mice livers were perfused, excised and the hepatocytes were separated from nonparenchymal cells and analysed in a fluorescence-activated cell sorter analyzer. The result was that hepatocytes took up significantly more liposomes when lactosylceramide was inserted in the liposome bilayers, which was in good agreement with observations made on the in vivo uptake of liposome-encapsulated insulin gene (Soriano, P. et al. (1983) Proc. Natl. Acad. Sci. USA, 80, 7128-7133). Cytofluorimetric analysis of the spleen cells showed that approx. 10% of the splenic lymphocytes take up high amounts of lactosylceramide liposomes, whereas most of the phospholipid liposomes are taken up by the phagocytic cells. The flow cytofluorimetric analysis shows, moreover, the internalization of the liposomes by the target cells and allows a quantitation of this uptake. Thus, in vivo targeting of the liposomes to specific liver and splenic cells, by means of glycolipid insertion in the liposome bilayer, is shown to take place with delivery of the liposomal aqueous space marker to these cells.
D000818:Animals; D005434:Flow Cytometry; D005452:Fluoresceins; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D010713:Phosphatidylcholines / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*
D005452:Fluoresceins; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C024098:6-carboxyfluorescein