RECEPTOR-MEDIATED DELIVERY OF DAUNOMYCIN USING IMMUNOLIPOSOMES - PHARMACOKINETICS AND TISSUE DISTRIBUTION IN THE RAT

Pharmacokinetics and tissue distribution of daunomycin and different l iposomal formulations of daunomycin were determined, Special emphasis was thereby given to immunoliposome-mediated drug delivery. Three diff erent types of 85 nm liposomes were used for this study: 1) convention al liposomes, 2) liposomes sterically stabilized with 2000 Dalton poly ethylene glycol and 3) immunoliposomes prepared by coupling a control IgG(2a) or monoclonal antibody to the distal end of the polyethylene g lycol spacer, The antibody used was the OX26 monoclonal antibody to th e rat transferrin receptor. Daunomycin and liposomes were administered by i.v. injection to the rat. Daunomycin and daunomycin in convention al liposomes were rapidly cleared from the plasma compartment, When co mpared to the free drug, daunomycin in conventional liposomes did accu mulate to higher levels in liver and spleen and to lower levels in hea rt, lung and liver, In contrast, daunomycin in liposomes sterically st abilized with polyethylene glycol could not be detected in heart, lung , kidney, liver and spleen. Using nonspecific IgG(2a) isotype immunoli posomes, tissue concentrations of immunoliposomes were reduced by at l east a factor of two, Attachment of more than 29 OX26 monoclonal antib odies 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 indic ate that receptor mediated drug delivery to different tissues can be a chieved using OX26 conjugated immunoliposomes.