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Biomed Khim ; 51(3): 276-86, 2005.
Article in Russian | MEDLINE | ID: mdl-16104390

ABSTRACT

PEGylated (stealth) immunoliposomes covalently linked to antibodies against human gliofibrillary acidic protein (GFAP) were prepared by coupling the thiolated monoclonal anti-GFAP antibodies, D4, with a maleimide derivative of the phosphatidyl ethanolamine of the liposomal membrane. Depending on the initial protein-to-lipid ratios, the immunoliposomes prepared (with a diameter of about 70 nm) were coupled with 60 to 240 molecules of the antibodies. In vitro experiments with cultures of the embryonic rat brain astrocytes demonstrated a specific binding of these immunoliposomes, which could be inhibited by the preincubation of the cells with free non-coupled D4 but not with non-specific antibodies. Administered intravenously into rats, the immunoliposomes exhibited a kinetic behaviour typical for the PEGylated liposomes: after 24 h, approximately 20% of the doses injected were still present in the blood; the elimination rate constants were 0.05-0.09 h(-1), the elimination half-lives were 8-15 h. With such a systemic longevity, as well as with such a specificity, these immunoliposomes, non-penetrating through intact blood-brain barrier (BBB), should be useful in delivering pharmacological agents to glial brain tumours (which continue to express GFAP) or to other pathological loci in the brain with a partially disintegrated BBB.


Subject(s)
Antibodies, Monoclonal/chemistry , Astrocytes/metabolism , Brain/cytology , Glial Fibrillary Acidic Protein/immunology , Liposomes/chemistry , Oligopeptides/administration & dosage , Polyethylene Glycols/chemistry , Animals , Antibodies, Monoclonal/metabolism , Cells, Cultured , Embryo, Mammalian/cytology , Glial Fibrillary Acidic Protein/metabolism , Iodine Radioisotopes , Oligopeptides/pharmacokinetics , Rats , Rats, Wistar
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