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Delivery Across the Blood-Brain Barrier

Innovative technologies enhancing the penetration of central nervous system drugs

CNS drugs are associated with longer development times and higher attrition rates than drugs for other therapy areas. Advances in delivery technologies are essential if the pursuit of novel treatments is to remain commercially viable


The blood-brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) exist to protect the brain, stringently regulating the passage of substances in and out. This report examines the ways in which these natural barriers may be overcome or circumvented to ensure that drugs can reach their intended target in the brain.

Features and benefits

  • Understand the functions of the blood-brain barrier and the reasons why it presents a significant challenge in development of CNS drugs.
  • Identify the five main strategies for maximizing the delivery of drugs to the brain.
  • Understand the scientific basis of the most promising and recent technology advances.
  • Identify the companies that are at the cutting edge of each type of delivery technology.
  • Assess which types of delivery technology are best suited to which types of drug and therapy area.

Key questions

  • Which delivery technologies can be considered for a drug that needs to achieve high CNS penetration?
  • What types of chemical modification have been applied and how successful have these been?
  • What role can nanotechnology play in CNS drug delivery?
  • How well validated are the delivery technologies and which are supported by data from human trials?
  • Are there in indications in which the problems of blood-brain barrier penetration can be circumvented by direct injection or implantation?

Key findings

Increasingly, drug delivery specialists are harnessing endogenous BBB mechanisms such as receptor-mediated delivery pathways with nano-enabled platform technologies to improve the uptake and targeted delivery of substances into the brain.

Improvements in intranasal delivery devices and advances in formulation technologies have enabled researchers to deliver a wide range of substances in therapeutic doses into the olfactory regions. Medical device companies Kurve Technology, Impel NeuroPharma, and OptiNose have all developed devices that are compatible with intranasal delivery.

Chemical modification (e.g. lipidation and cationization) can be used to improve passive delivery across the blood-brain barrier but is rarely used in isolation. Permeability enhancers can be used to transiently disrupt the BBB to allow the passage of drugs into the CNS, but they have yet to be fully validated in the clinic.

Coverage: global

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