title: [Production and characteristics of PEGylated immunoliposome transport vectors specific for neural tissue astrocytes].
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.
authors.forename: V P
authors.initials: VP
authors.lastname: Chekhonin
authors.forename: Iu A
authors.initials: IuA
authors.lastname: Zhirkov
authors.forename: O I
authors.initials: OI
authors.lastname: Gurina
authors.forename: S V
authors.initials: SV
authors.lastname: Lebedev
authors.forename: T B
authors.initials: TB
authors.lastname: Dmitrieva
authors.forename: A V
authors.initials: AV
authors.lastname: Semenova
authors.forename: T V
authors.initials: TV
authors.lastname: Iaglova
authors.forename: A E
authors.initials: AE
authors.lastname: Riabinina
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008081:Liposomes / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D007457:Iodine Radioisotopes; D008081:Liposomes; C504419:Lys-Tyr-Lys-Pro-Lys-Tyr-Asp; D009842:Oligopeptides; D011092:Polyethylene Glycols