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Intraparenchymal Delivery and Its Discontents

  • Raghu Raghavan
Protocol
Part of the Neuromethods book series (NM, volume 45)

Abstract

In the treatment of central nervous system diseases, therapeutic particles need to breach the blood–brain barrier (BBB) to reach their intended target, and it has long been known that this is a difficult barrier to breach. The barrier is both passive with tight junctions hindering passage of even rather small molecules, as well as active with transporters that can pump select molecules back into the bloodstream. The diseases include both those where this barrier has been compromised such as brain tumors, hemorrhagic stroke, and neurotrauma; as well as neurodegenerative disorders where the compromise is substantially less and often unnoticeable. In addition to the pharmaceutical solution which involves design of small molecules that may be administered orally or at least systemically, there is also a compelling need at present to design devices for direct delivery of therapeutics into the central nervous system. Such delivery methods are unpopular because of their intrusiveness; however, the lack of success of the systemic route in the treatment of many of the most severe brain diseases has established a need for such devices, and the success and popularity of deep brain stimulation (DBS) has lowered the psychological barrier to these. Many clinical trials are under way which demand direct delivery of therapeutics to the brain. Such therapeutics range from small molecules, large proteins, nanoparticles, and viral carriers for gene therapies, to cells. This chapter is a review of intraparenchymal delivery of such therapies for brain diseases and of the devices used for such purposes.

Key words

Intracerebral drug delivery convection-enhanced delivery infusion brain intraparenchymal catheters catheters 

Notes

Acknowledgement

The research described in this paper was supported in part by the Kinetics Foundation. Most of the figures have been obtained during collaborative research with a number of collaborators. These collaborators have been mentioned in the figure captions and I owe them a debt of gratitude in permitting use of the figures in this chapter. The title of course is borrowed from a well-known source (78).

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Raghu Raghavan
    • 1
  1. 1.Therataxis, LLCBaltimoreUSA

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