Stability in biological fluids and clearance of immunoliposomes.
The in vivo and in vitro stability of liposomes having covalently bound monoclonal antibodies (MAB) connected to their surface via a disulfide bridge (about 6 anti-melanoma MAB-molecules per liposome) in tissue fluids was investigated. These immunoliposomes were composed of equimolar amounts of hydrogenated soybean lecithin and cholesterol and had a mean diameter of 113 nm. The protein-lipid binding, change of vesicle size and the release of encapsulated carboxyfluorescein (CF) were estimated. After i.v. injection into mice, an initial protein cleavage of 21% occurred within 30 min p.a., followed by a slow elimination of intact MAB-liposomes from blood circulation (t50 = 2.2 h). These liposomes had a similar elimination rate as protein-free liposomes. The in vitro results after incubation of MAB-liposomes in blood, plasma, serum and tissue fluid were very similar with regard to the protein-lipid cleavage, but the time dependence was different. The CF-release in vitro was slower (about 1.5%/d) than the protein cleavage; the vesicle size of MAB-liposomes increased substantially in contrast to protein-free liposomes in serum during 4 days.
Institute of Pharmaceutical Technology and Biopharmaceutics, University of Heidelberg, Fed. Rep. of Germany.
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Weckenmann
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Matzku
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Stricker
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Sinn
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000032:analysis; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D008081:Liposomes / Q000097:blood / Q000276:immunology* / Q000652:urine; D051379:Mice; D011817:Rabbits
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D008081:Liposomes