Immunospecific targeting of immunoliposomes, F(ab')2 and IgG to red blood cells in vivo.
In this report a model to study the fate of target cells in the blood circulation after injection of appropriate immunoliposomes is discussed. The effect of intravenous administration of antimouse RBC immunoliposomes, F(ab')2 or IgG on the fate of intravenously injected 51Cr-labelled mouse RBC (Cr-mRBC) in the mouse and, particularly, in the rat was studied. The immunoliposome was of the Fab'-MPBPE-REV type (Fab'-fragments covalently linked to reverse phase evaporation vesicles by maleimido-4-(p-phenylbutyrate)phosphatidylethanolamine). In the rat model a high blood level (80%) of the injected dose of target cells, Cr-mRBC, was maintained for several hours. The elimination by Fab'-liposomes, F(ab')2 or IgG of Cr-mRBC, and subsequent uptake into liver and spleen was dose dependent. Administration of Fab'-liposomes or F(ab')2 resulted in a preferential uptake into the spleen (above a certain dose also, but much lower, uptake into the liver was observed), while after IgG administration 51Cr-label was mainly recovered in the liver. At equal protein doses (+/- 130 micrograms) Fab'-liposomes induced a faster elimination of the Cr-mRBC and a higher uptake into the spleen than F(ab')2. The potential advantage of the use of drug-loaded immunoliposomes to eliminate target cells from the blood stream and to induce a certain pharmacological effect in the target cells, in comparison with the free antibody administration of F(ab')2 or IgG is discussed.
Peeters
P A
PA
Department of Pharmaceutics, Faculty of Pharmacy, State University of Utrecht, The Netherlands.
Oussoren
C
C
Eling
W M
WM
Crommelin
D J
DJ
D000818:Animals; D002860:Chromium Radioisotopes; D004912:Erythrocytes / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage* / Q000276:immunology; D008099:Liver / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D051381:Rats; D013154:Spleen / Q000276:immunology
D002860:Chromium Radioisotopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008081:Liposomes