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Neurosurgical Approaches: Drug Infusion Directly into the Parenchyma or the Cerebrospinal Fluid

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

Abstract

Delivering drugs effectively to the central nervous system (CNS) has always presented a challenge. The blood–brain barrier prevents significant amounts of systemically administered therapeutics from reaching the brain. Traditional local CNS delivery (e.g., biodegradable polymers, cerebro-ventricular injection, cell implantation) has relied on diffusion, which is dependent on a concentration gradient. The rate of diffusion is inversely proportional to the size of the agent and is usually slow with respect to tissue clearance, resulting in a non-homogeneous distribution often restricted to a few millimeters from the source. By contrast, convection-enhanced delivery uses a pressure gradient established at the tip of an infusion catheter to create bulk flow, “pushing” drugs into a large volume of brain tissue. This displacement allows the infused material to engage the vasculature, with rhythmic blood vessel contractions acting as an efficient motive force to move particles along perivascular tracts. This chapter describes a fully integrated and FDA-approved drug delivery system for cerebral infusion that consists of an MR-compatible aiming device, a reflux-resistant cannula, and predictive software, allowing the monitoring of nanoparticle, viral vector, or small molecule distribution in “real time” during brain and brain tumor delivery.

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Authors and Affiliations

  1. University of California, San Francisco, CA, USA

    Krystof Bankiewicz

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  1. Krystof Bankiewicz
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Correspondence to Krystof Bankiewicz .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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Bankiewicz, K. (2014). Neurosurgical Approaches: Drug Infusion Directly into the Parenchyma or the Cerebrospinal Fluid. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_18

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