Review: Brain drug targeting: The future of brain drug development

William A. Pardridge
Cambridge University Press, Inc., 2001, 353 pages

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Book cover image Although some could argue that it places excessive emphasis on the author's own studies, Brain Drug Targeting brings a healthy skepticism to the study of the blood-brain barrier (BBB), which is the most frustrating obstacle for pharmacologists wishing to find treatments for brain disorders. Well-organized, up to date, and expertly written by an well-known researcher in the field who has worked and written books on the blood-brain barrier for many years, the emphasis of this book is on pharmacological and physiological aspects of the BBB; relatively little is known at the biochemical level about signal transduction pathways and protein phosphorylation specific to the blood-brain barrier, and these topics are clearly outside the author's area of expertise.

The use of liposomes and nanoparticles to transport drugs across the BBB has a particularly checkered history, with some studies having coinjected Polysorbate 80, a detergent that can disrupt the BBB, with the drug as a stabilizing agent, and incorrectly attributing the detergent effects to their own nanoparticles. In other studies, the large size of the liposomes that were used produced microembolisms that gave a false impression of brain uptake.

The study by Huwyler in the author's lab, in which OX26-MAb conjugated pegylated immunoliposomes were injected in attempts to transport daunomycin through the BBB, illustrates the difficulty researchers have experienced with this approach. Almost all the rhodamine label from rhodamine-conjugated phosphatidyl ethanolamine was found to be localized to capillary endothelial cells. The author's paper, discussed in the book, that demonstrated endocytosis of immunoliposomes into cultured RG2 glioma cells was an important milestone. However, the problem of getting agents across the BBB and into the brain parenchyma still remains.

Other chapters discuss receptor-mediated transcytosis of peptides, chimeric peptides, and linker strategies such as avidin-biotin conjugates, pegylation technology, and antisense neurotherapeutics, using data from the author's laboratory to illustrate typical results.

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June 30, 2002 Back