Evaluation of hepatotropic targeting properties of allogenic and xenogenic erythrocyte ghosts in normal and liver-injured rats.
OBJECTIVE
Haemoglobin-depleted erythrocyte ghosts have been recommended as vesicle carriers of drugs with hepatotropic properties. However, the influence of liver injury on ghost elimination and targeting has not been reported so far.


METHODS
Human and rat ghosts were prepared and loaded with model substances, and the basic parameters were characterized. Ghosts were injected intravenously into rats with acute, subacute and chronic liver injuries. Elimination from circulation, organ distribution and cellular targeting was measured. The uptake of ghosts by liver macrophages/Kupffer cells was determined in cell culture.


RESULTS
Ghosts are strong hepatotropic carriers with a recovery of 90% in normal liver. Kupffer cells are the almost exclusive target cell type. Hepatotropic properties remain in rats with chronic liver diseases, but are reduced by 60-70% in acute liver damage as a result of decline of phagocytosis of macrophages/Kupffer cells. Although the uptake of ghosts per gram liver tissue in chronic liver injury was also reduced by about 40%, the increase of liver mass and of macrophages/Kupffer cells compensated for the reduced phagocytotic activity. In subacute injury, the uptake per gram liver tissue was only moderately reduced.


CONCLUSIONS
Drug targeting with ghosts might be feasible in chronic and subacute liver injuries, e.g. fibrogenesis and tumours, because the content of ingested ghosts is released by Kupffer cells into the micro-environment, providing the uptake by and pharmacological effects on adjacent cells.
Gressner
Olav A
OA
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Aachen, Germany. agressner@ukaachen.de
Lahme
Birgit
B
Koch
Martin
M
Gressner
Axel M
AM
D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000637:transplantation*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009439:Neuraminidase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium
D013667:Technetium; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D009439:Neuraminidase