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In Vitro Models of CNS Barriers

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Drug Delivery to the Brain

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

Abstract

This chapter reviews the history and modern applications of isolated preparations of the three main CNS barrier layers and cell culture preparations derived from them. In vitro models give valuable mechanistic information but also provide useful assay systems for drug discovery and delivery programmes. However, it is important to take into account practical issues including species differences and the degree to which the differentiated state of the in vivo barrier is retained. The range of models available is reviewed, with a critical evaluation of their strengths and weaknesses, and guidance in selecting and optimizing a suitable model for particular applications. New understanding of the unstirred water layers and paracellular leak pathway in in vitro preparations gives greater insights into the “intrinsic permeability” of the membrane, and a variety of techniques permit characterization of the transport systems and enzymes contributing to barrier function. Increasingly, aspects of CNS pathology are being modelled in cell culture, aiding the optimization of drug delivery regimes in pathological conditions.

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Acknowledgements

We are grateful for discussions and comments from many colleagues especially Dr. Alex Avdeef, and Prof Margareta Hammarlund-Udenaes; for redrawing of Fig. 6.1 by Dr. Robert Thorne; and for Fig. 6.4 from Dr. Anika Hartz and Dr. Björn Bauer.

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Authors and Affiliations

  1. BBB Group, Institute of Pharmaceutical Science, King’s College London, Franklin Wilkins Building 3.10, 150 Stamford St, London, SE1 9NH, UK

    N. Joan Abbott & Diana E. M. Dolman

  2. HICoE Centre for Drug Research, Universiti Sains Malaysia, Minden, Penang, 11800, Malaysia

    Siti R. Yusof

  3. Bayer Pharma AG, Global Drug Discovery, DMPK, Berlin, D-13353, Germany

    Andreas Reichel

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  1. N. Joan Abbott
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  2. Diana E. M. Dolman
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  3. Siti R. Yusof
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  4. Andreas Reichel
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Correspondence to N. Joan Abbott .

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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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Abbott, N.J., Dolman, D.E.M., Yusof, S.R., Reichel, A. (2014). In Vitro Models of CNS Barriers. 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_6

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