TY - JOUR
T1 - In vitro models of CNS barriers
AU - Abbott, N. Joan
AU - Dolman, Diana E.M.
AU - Yusof, Siti R.
AU - Reichel, Andreas
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081145886&partnerID=8YFLogxK
U2 - 10.1007/978-1-4614-9105-7_6
DO - 10.1007/978-1-4614-9105-7_6
M3 - Article
AN - SCOPUS:85081145886
SN - 2210-7371
VL - 10
SP - 163
EP - 197
JO - AAPS Advances in the Pharmaceutical Sciences Series
JF - AAPS Advances in the Pharmaceutical Sciences Series
ER -