Considerations When Developing Blood-Brain Barrier Crossing Drug Delivery Technology

• Published in: Handbook of experimental pharmacology Vol. 273; p. 83
• Main Author: Bell, Robert D
• Format: Journal Article
• Language: English
• Published: Germany 2022
• Subjects: Biological Transport; Blood-Brain Barrier - metabolism; Brain - metabolism; Drug Delivery Systems; Humans; Pharmaceutical Preparations - metabolism; Technology; Pericyte; Glycocalyx; Endothelial; Blood–brain barrier (BBB); Drug delivery; Neurotrophic; Gene therapy; Central nervous system (CNS); Transferrin receptor
• ISSN: 0171-2004
• DOI: 10.1007/164_2021_453

Efficient therapeutic transport across the neurovasculature remains a challenge for developing medicine to treat central nervous system (CNS) disorders (Bell and Ehlers, Neuron 81:1-3, 2014). This chapter is meant to provide some insight and key considerations for developing and evaluating various technologies and approaches to CNS drug delivery. First, a brief review of various biological barriers, including the immune system, cellular and protein components of the blood-brain barrier (BBB), and clearance mechanisms in peripheral organs is provided. Next, a few examples and learnings from existing BBB-crossing modalities will be reviewed. Insight from "BBBomic" databases and thoughts on basic requirements for successful in vivo validation studies are discussed. Finally, an additional engineering barrier, namely manufacturing and product scalability, is highlighted as it relates to clinical translation and feasibility for developing BBB-crossing delivery technologies. A goal of this chapter is to provide an overview of the many barriers to the successful delivery of medicines into the brain. An emphasis will be placed on biotherapeutic and gene therapy applications for the treatment of neurological and neurodegenerative disorders.