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Int J Mol Sci. 2019 Jun 25;20(12). pii: E3108. doi: 10.3390/ijms20123108.

Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis.

Author information

1
Medical and Biological Sciences Building, School of Biology, University of St Andrews, St Andrews KY16 9TF, UK. rar5@st-andrews.ac.uk.
2
Biomedical Science Research Centre, Schools of Chemistry and Biology, University of St Andrews, St Andrews KY16 9TF, UK. rar5@st-andrews.ac.uk.
3
Biomedical Science Research Centre, Schools of Chemistry and Biology, University of St Andrews, St Andrews KY16 9TF, UK. gjf1@st-andrews.ac.uk.
4
Medical and Biological Sciences Building, School of Biology, University of St Andrews, St Andrews KY16 9TF, UK. fjg1@st-andrews.ac.uk.
5
Biomedical Science Research Centre, Schools of Chemistry and Biology, University of St Andrews, St Andrews KY16 9TF, UK. fjg1@st-andrews.ac.uk.

Abstract

Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS is presented. This classification includes the use of formulations administered systemically that can elicit transcytosis-mediated transport by interacting with transporters expressed by transvascular endothelial cells. Neurotherapeutics can also be delivered to the CNS by means of surgical intervention using specialized catheters or implantable reservoirs. Strategies for delivering drugs to the CNS have evolved tremendously during the last two decades, yet, some factors can affect the quality of data generated in preclinical investigation, which can hamper the extension of the applications of these strategies into clinically useful tools. Here, we disclose some of these factors and propose some solutions that may prove valuable at bridging the gap between preclinical findings and clinical trials.

KEYWORDS:

Blood-brain barrier; CNS-targeted drug delivery; Efflux-pump inhibition; Receptor-mediated transcytosis; Ring-opening metathesis polymerization; Transient BBB disruption

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