Receptor mediated delivery of daunomycin using immunoliposomes: pharmacokinetics and tissue distribution in the rat.
Pharmacokinetics and tissue distribution of daunomycin and different liposomal formulations of daunomycin were determined. Special emphasis was thereby given to immunoliposome-mediated drug delivery. Three different types of 85 nm liposomes were used for this study: 1) conventional liposomes, 2) liposomes sterically stabilized with 2000 Dalton polyethylene glycol and 3) immunoliposomes prepared by coupling a control IgG2a or monoclonal antibody to the distal end of the polyethylene glycol spacer. The antibody used was the OX26 monoclonal antibody to the rat transferrin receptor. Daunomycin and liposomes were administered by i.v. injection to the rat. Daunomycin and daunomycin in conventional liposomes were rapidly cleared from the plasma compartment. When compared to the free drug, daunomycin in conventional liposomes did accumulate to higher levels in liver and spleen and to lower levels in heart, lung and liver. In contrast, daunomycin in liposomes sterically stabilized with polyethylene glycol could not be detected in heart, lung, kidney, liver and spleen. Using nonspecific IgG2a isotype immunoliposomes, tissue concentrations of immunoliposomes were reduced by at least a factor of two. Attachment of more than 29 OX26 monoclonal antibodies per liposome did not increase tissue levels in heart, kidney or lung. Tissue levels of OX26 immunoliposomes were reduced in all organs by coinjection of unbound OX26. In vitro, endocytosis of fluorescent immunoliposomes by RG2 rat glioma cells was observed. These data indicate that receptor mediated drug delivery to different tissues can be achieved using OX26 conjugated immunoliposomes.
Huwyler
J
J
Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1682, USA.
Yang
J
J
Pardridge
W M
WM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003630:Daunorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005910:Glioma / Q000378:metabolism; D008081:Liposomes; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000276:immunology / Q000502:physiology*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D011990:Receptors, Transferrin; D011092:Polyethylene Glycols; D003630:Daunorubicin