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.
Chekhonin V.P. et al. Pegylated immunoliposomes directed against embryonal rat brain astrocytes // Biomeditsinskaya Khimiya. - 2005. - V. 51. -N 3. - P. 276-286.
Chekhonin V.P. et al., "Pegylated immunoliposomes directed against embryonal rat brain astrocytes." Biomeditsinskaya Khimiya 51.3 (2005): 276-286.
Chekhonin, V. P., Zhirkov, Yu. A., Gurina, O. I., Lebedev, S. V., Dmitriyeva, T. B., Semenova, A. V., Jaglova, T. V., Rjabinina, , A. E. (2005). Pegylated immunoliposomes directed against embryonal rat brain astrocytes. Biomeditsinskaya Khimiya, 51(3), 276-286.
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