Delivery Across the Blood-Brain Barrier

Dallas, TX -- (SBWIRE) -- 09/11/2012 -- 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?
- 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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Table of Contents

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

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 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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