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Osmotic Opening of the BBB for Drug Treatment of Brain Tumors (Focus on Methodological Issues)

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

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Abstract

The blood–brain barrier (BBB) is a complex, functional barrier composed of endothelial cells, pericytes, astrocytic endfeet, and neuronal cells. This highly organized unit expresses a selective permeability for molecules that possess adequate molecular weight and sufficient liposolubility. Unfortunately, many potential therapeutic agents do not cross the BBB. As the BBB limitation has become more and more acknowledged, many innovative surgical and pharmacological strategies have been developed to circumvent it. This chapter focuses on the osmotic opening of the BBB. Since its inception by Rapoport in 1972, preclinical studies have provided important information on the extent of BBB permeation using this strategy. Neuwelt and colleagues further developed the osmotic opening of the BBB and brought it to the clinic. However, many questions remain as to the detailed physiology of the procedure, its long-term physiological impacts, and its best application to the clinic. Here we describe the results from ongoing studies relating to the spatial and temporal distribution of molecules after osmotic BBB breaching as well as the window of BBB permeabilization. We also summarize recent clinical series highlighting promising results in the application of this procedure. Finally, we discuss different approaches used to maximize the reach and efficacy of the procedure as well as to measure its physiological impact.

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Authors and Affiliations

  1. Department of Neurosurgery and Neuro-oncology, Université de Sherbrooke, Sherbrooke, QC, Canada, J1K 2R1

    David Fortin M.D., F.R.C.S.C.

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  1. David Fortin M.D., F.R.C.S.C.
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Correspondence to David Fortin M.D., F.R.C.S.C. .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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Fortin, D. (2014). Osmotic Opening of the BBB for Drug Treatment of Brain Tumors (Focus on Methodological Issues). In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_19

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