Abstract
The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.
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Notes
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Acknowledgements
No funding was provided to assist in the preparation of this review. Albertus G. de Boer is the Chairman of the scientific advisory board and Pieter J. Gaillard is the CEO of to-BBB technologies BV, Leiden, The Netherlands (which is developing CRM197). Both authors own stocks in to-BBB technologies BV, have received grants on the CRM197 technology and are co-inventors on patent applications covering the use of CRM197 technology.
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de Boer, A.G., Gaillard, P.J. Strategies to Improve Drug Delivery Across the Blood-Brain Barrier. Clin Pharmacokinet 46, 553–576 (2007). https://doi.org/10.2165/00003088-200746070-00002
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DOI: https://doi.org/10.2165/00003088-200746070-00002