4.8 Review

Strategies for delivering therapeutics across the blood-brain barrier

Journal

NATURE REVIEWS DRUG DISCOVERY
Volume 20, Issue 5, Pages 362-383

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41573-021-00139-y

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The blood-brain barrier presents a challenge for delivering therapeutics to the central nervous system, particularly for biopharmaceuticals. Non-invasive approaches have been developed to help overcome this challenge, with increasing research efforts focusing on technologies to deliver therapeutics to the CNS, some of which have entered clinical testing. Developing effective strategies for crossing the blood-brain barrier is crucial for treating CNS disorders, with a particular emphasis on non-invasive methods such as receptor-mediated transcytosis and the use of neurotropic viruses, nanoparticles, and exosomes.
The blood-brain barrier is a perennial challenge for the delivery of therapeutics to the central nervous system. In their Review, Terstappen and colleagues discuss non-invasive approaches to brain delivery, particularly for biopharmaceuticals, some of which are now in clinical testing. Achieving sufficient delivery across the blood-brain barrier is a key challenge in the development of drugs to treat central nervous system (CNS) disorders. This is particularly the case for biopharmaceuticals such as monoclonal antibodies and enzyme replacement therapies, which are largely excluded from the brain following systemic administration. In recent years, increasing research efforts by pharmaceutical and biotechnology companies, academic institutions and public-private consortia have resulted in the evaluation of various technologies developed to deliver therapeutics to the CNS, some of which have entered clinical testing. Here we review recent developments and challenges related to selected blood-brain barrier-crossing strategies - with a focus on non-invasive approaches such as receptor-mediated transcytosis and the use of neurotropic viruses, nanoparticles and exosomes - and analyse their potential in the treatment of CNS disorders.

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