Pegylated immunoliposomes directed against embryonal rat brain astrocytes

   


1. Laboratory of Immunochemistry, Serbsky National Research Center for Social and Forensic Psychiatry
2. Insitute of Protein Research, Russian Academy of Sciences
Type: Experimental/clinical study
PubMed Id: 16104390
Year: 2005 vol: 51  issue:3  pages: 276-286
Abstract: PEGylated (stealth) immunoliposomes covalently linked to antibodies against humal 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 initial protein-to-lipid rations, 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 behavior 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.
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Reference: Chekhonin V.P., Zhirkov Yu.A., Gurina O.I., Lebedev S.V., Dmitriyeva T.B., Semenova A.V., Jaglova T.V., Rjabinina A.E., Pegylated immunoliposomes directed against embryonal rat brain astrocytes, Biomeditsinskaya khimiya, 2005, vol: 51(3), 276-286.
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