Tools for studying drug transport and metabolism in the brain

ABSTRACT

Introduction: Development of xenobiotics that cross the blood-brain barrier in therapeutically-relevant quantities is an expensive and time-consuming undertaking. However, central nervous system diseases are an under-addressed cause of high mortality and morbidity, and drug development in this field is a worthwhile venture.

Areas covered: We aim to familiarize the reader with available methodologies for studying drug transport into the brain. Current understanding of the blood-brain barrier structure has been well-described in other manuscripts, and first we briefly review the path that xenobiotics take through the brain – from bloodstream, to endothelial cells of the blood-brain barrier, to interstitial space, to brain parenchymal cells, and then to an exit point from the central nervous system. The second half of the review discusses research tools available to determine if xenobiotics are making the journey through the brain successfully and offers commentary on the translational utility of each methodology.

Expert opinion: Theoretically, non-human mammalian and human blood-brain barriers are similar in composition; however, some findings demonstrate important differences across species. Translational methodologies may provide more reliable information about how a drug may act across species. The recent finding of lymphatic vessels within the central nervous system may provide new tools and strategies for drug delivery to the brain.

KEYWORDS:

• Blood-brain barrier
• cerebrospinal fluid
• drug transport
• microdialysis
• neuroimaging

Acknowledgements

We thank Dr Lawrence Maness for helpful discussions in the preparation of this manuscript.

Declaration of Interest

The Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, The University of Texas McGovern Medical School at Houston. Laboratory of Neurosciences (Brazil) is one of the centers of the National Institute for Molecular Medicine (INCT-MM) and one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). Its research is supported by grants from CNPq (J De Quevedo); FAPESC (J De Quevedo); Instituto Cérebro e Mente (J De Quevedo) and UNESC (J De Quevedo). J De Quevedo is a 1A CNPq Research Fellow. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.