Receptor Mediated Delivery of Daunomycin Using Immunoliposomes: Pharmacokinetics and Tissue Distribution in the Rat

作者: William M. Pardridge , Jörg Huwyler , Jing Yang

DOI:

关键词:

摘要: Pharmacokinetics and tissue distribution of daunomycin different liposomal formulations were determined. Special emphasis was thereby given to immunoliposome-mediated drug delivery. Three types 85 nm liposomes used for this study: 1) conventional liposomes, 2) sterically stabilized with 2000 Dalton polyethylene glycol 3) immunoliposomes prepared by coupling a control IgG2a or monoclonal antibody the distal end spacer. The OX26 rat transferrin receptor. Daunomycin administered i.v. injection rat. in rapidly cleared from plasma compartment. When compared free drug, did accumulate higher levels liver spleen lower heart, lung liver. In contrast, could not be detected lung, kidney, spleen. Using nonspecific isotype immunoliposomes, concentrations reduced at least factor two. Attachment more than 29 antibodies per liposome increase kidney lung. Tissue all organs coinjection unbound OX26. vitro, endocytosis fluorescent RG2 glioma cells observed. These data indicate that receptor mediated delivery tissues can achieved using conjugated immunoliposomes.

参考文章(31)
Noam Emanuel, Eli Kedar, Elijah M. Bolotin, Nechama I. Smorodinsky, Yechezkel Barenholz, Preparation and characterization of doxorubicin-loaded sterically stabilized immunoliposomes. Pharmaceutical Research. ,vol. 13, pp. 352- 359 ,(1996) , 10.1023/A:1016028106337
W A Jefferies, S V Hunt, A F Williams, M R Brandon, Analysis of lymphopoietic stem cells with a monoclonal antibody to the rat transferrin receptor. Immunology. ,vol. 54, pp. 333- 341 ,(1985)
Koichiro Matsukado, Keith L. Black, Shin Nakano, Increased Brain Tumor Microvessel Permeability after Intracarotid Bradykinin Infusion Is Mediated by Nitric Oxide Cancer Research. ,vol. 56, pp. 4027- 4031 ,(1996)
Rudy L. Juliano, Dennis Stamp, Pharmacokinetics of liposome-encapsulated anti-tumor drugs Biochemical Pharmacology. ,vol. 27, pp. 21- 27 ,(1978) , 10.1016/0006-2952(78)90252-6
W M Pardridge, P M Friden, L R Walus, R M Starzyk, Enhanced uptake of rsCD4 across the rodent and primate blood-brain barrier after conjugation to anti-transferrin receptor antibodies. Journal of Pharmacology and Experimental Therapeutics. ,vol. 277, pp. 1067- 1075 ,(1996)
W. M. Pardridge, R. J. Boado, Y. S. Kang, Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 5592- 5596 ,(1995) , 10.1073/PNAS.92.12.5592
GREGORY GREGORIADIS, JUDITH SENIOR, BARBARA WOLFF, CHRISTOPHER KIRBY, Targeting of Liposomes to Accessible Cells In Vivo Annals of the New York Academy of Sciences. ,vol. 446, pp. 319- 339 ,(1985) , 10.1111/J.1749-6632.1985.TB18411.X
J. Huwyler, D. Wu, W. M. Pardridge, Brain drug delivery of small molecules using immunoliposomes Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 14164- 14169 ,(1996) , 10.1073/PNAS.93.24.14164
J. Rosenecker, W. Zhang, K. Hong, J. Lausier, P. Geppetti, S. Yoshihara, D. Papahadjopoulos, J. A. Nadel, Increased Liposome Extravasation in Selected Tissues: Effect of Substance P Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 7236- 7241 ,(1996) , 10.1073/PNAS.93.14.7236