Delivery Across the Blood-Brain Barrier


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Delivery Across the Blood-Brain Barrier

  1. 1. Delivery Across the Blood-Brain BarrierReport Details:Published:September 2012No. of Pages: 84Price: Single User License – US$3800The blood-brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) exist to protectthe brain, stringently regulating the passage of substances in and out. This report examines theways in which these natural barriers may be overcome or circumvented to ensure that drugs canreach 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.HighlightsIncreasingly, drug delivery specialists are harnessing endogenous BBB mechanisms such asreceptor-mediated delivery pathways with nano-enabled platform technologies to improve theuptake and targeted delivery of substances into the brain.Improvements in intranasal delivery devices and advances in formulation technologies haveenabled researchers to deliver a wide range of substances in therapeutic doses into the olfactoryregions. Medical device companies Kurve Technology, Impel NeuroPharma, and OptiNose haveall developed devices that are compatible with intranasal delivery.Chemical modification (e.g. lipidation and cationization) can be used to improve passive deliveryacross the blood-brain barrier but is rarely used in isolation. Permeability enhancers can be usedto transiently disrupt the BBB to allow the passage of drugs into the CNS, but they have yet to befully 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. 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?Get your copy of this report @ 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. 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 conclusionsFuture outlook Summary Challenges and opportunities Stem cell and gene therapies Diamyd Medical AB NsGene A/S Neurologix Stem cell and gene therapy conclusions Overall conclusionsAppendix Scope Methodology Acknowledgements Abbreviations Bibliography/references Chapter 1 references Chapter 2 references Chapter 3 referencesTABLES Table: Products approved for intrathecal delivery Table: Inhibitors of blood-brain barrier efflux transporters Table: Receptor-mediated targeting ligandsFIGURES Figure: Schematic comparison of (A) brain capillary, (B) normal capillary, and (C) capillary in
  4. 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 devicesContact: for more information.