Strategies for delivering therapeutics across the blood–brain barrier

• Published in: Nature reviews. Drug discovery Vol. 20; no. 5; pp. 362 - 383
• Main Authors: Terstappen, Georg C., Meyer, Axel H., Bell, Robert D., Zhang, Wandong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2021; Nature Publishing Group
• Subjects: 631/154/152; 631/378/1341; Adenosine; Antibodies; Biomedical and Life Sciences; Biomedicine; Biopharmaceutics; Biotechnology; Biotechnology industry; Blood-brain barrier; Brain cancer; Cancer Research; Central nervous system agents; Dosage and administration; Drug delivery systems; Drugs; Endothelium; Feasibility studies; Health aspects; Medicinal Chemistry; Molecular Medicine; Nervous system; Neurosurgery; Permeability; Pharmaceutical industry; Pharmaceutical research; Pharmacology/Toxicology; Product development; Review Article; Tumors; Ultrasonic imaging; Vehicles; United States
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/s41573-021-00139-y

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. 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.