'New JMS features in GlassFish 4.0' by Nigel Deakin
Delivery Across the Blood-Brain Barrier
1. Delivery Across the Blood-Brain Barrier
Report Details:
Published:September 2012
No. of Pages: 84
Price: Single User License – US$3800
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.
Highlights
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.
Your key questions answered:
•Which delivery technologies can be considered for a drug that needs to achieve high CNS
penetration?
2. •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?
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Major points covered in Table of Contents of this report include
EXECUTIVE SUMMARY
Key findings
Why the blood-brain barrier matters in drug development
Summary
Introduction
Delivering drugs to the brain
The blood-brain barrier
The blood cerebrospinal fluid barrier
Transportation across the BBB
Neurosurgical
Pharmacological and physiological
CNS delivery issues
Oral and parenteral delivery
Intranasal delivery
Strategies for drug delivery to the brain
Summary
Delivery of drugs across the BBB
Direct injection and implantation
Conclusions on direct injection and implantation
Chemical modifications
Lipidation
Cationization
Prodrugs
CNS "locked" prodrugs
Carrier-mediated prodrugs
Receptor-mediated prodrugs
Conclusions on chemical modifications
Permeability enhancers
Efflux transporter inhibitors
Conclusions on permeability enhancers
3. Nano-enabled delivery technologies
Liposomes
Case study: G-Technology (to-BBB Technologies BV)
Bolaamphiphiles
Case study: V-Smart technology (Lauren Sciences)
Nanoparticles
Receptor-mediated delivery technologies
Case study: EPiC technology (Angiochem)
Other receptor-mediated delivery technologies
Conclusions on nano-enabled and receptor-mediated delivery technologies
Intranasal delivery
Mechanism of intranasal delivery
Intranasal delivery of biopharmaceuticals
Intranasal formulations
Intranasal devices
Case study: POD device (Impel NeuroPharma)
Intranasal conclusions
Overall conclusions
Future outlook
Summary
Challenges and opportunities
Stem cell and gene therapies
Diamyd Medical AB
NsGene A/S
Neurologix
Stem cell and gene therapy conclusions
Overall conclusions
Appendix
Scope
Methodology
Acknowledgements
Abbreviations
Bibliography/references
Chapter 1 references
Chapter 2 references
Chapter 3 references
TABLES
Table: Products approved for intrathecal delivery
Table: Inhibitors of blood-brain barrier efflux transporters
Table: Receptor-mediated targeting ligands
FIGURES
Figure: Schematic comparison of (A) brain capillary, (B) normal capillary, and (C) capillary in
4. choroid plexus
Figure: Schematic of drug transport pathways into the brain
Figure: Delivery strategies for brain drug delivery
Figure: Oral and intravenous drug profiles
Figure: Enhancing lipophilicity may increase CNS delivery
Figure: Schematic of the prodrug approach for CNS delivery
Figure: Chemical structures of both exogenous and endogenous LAT substrates
Figure: Schematic of G-Technology
Figure: Schematic of nose-to-brain pathways for drugs
Figure: Intranasal delivery devices
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