Strategies to Enhance the Distribution of Therapeutic Nanoparticles in the Brain by Convection Enhanced Delivery

Karina Negron, Namir Khalasawi, Jung Soo Suk

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Convection enhanced delivery (CED) is an attractive method to bypass the blood-brain barrier for therapeutic delivery to the brain as well as to facilitate widespread therapeutic distribution within brain parenchyma by creating a continuous pressure-driven bulk flow. However, rapid removal of therapeutics from the brain by the physiological clearance mechanism remains a critical challenge to achieving widespread therapeutic delivery by CED. Nanoparticle (NP)-based delivery systems that stay longer in the brain while convoying a high concentration of payloads can potentially provide widespread and efficient therapeutic delivery to the highly disseminated disease areas within the brain. In particular, we have recently demonstrated that CED of NPs designed to efficiently penetrate the highly adhesive and nanoporous brain extracellular matrix synergistically enhances the payload distribution within healthy and tumor-bearing brains. In this book chapter, we first briefly overview the mechanism and current limitations of CED, as well as strategies to maximize the CED-mediated therapeutic and/or NP delivery to the brain. We then describe a detailed methodology for preclinical CED experiments, including device/animal setup, NP preparation, tissue processing, and image/data analysis. Finally, we conclude the chapter with a few troubleshooting tips.

Original languageEnglish (US)
Title of host publicationNeuromethods
PublisherHumana Press Inc.
Pages179-204
Number of pages26
DOIs
StatePublished - 2021

Publication series

NameNeuromethods
Volume163
ISSN (Print)0893-2336
ISSN (Electronic)1940-6045

Keywords

  • Brain parenchyma
  • Brain-penetrating nanoparticles
  • Infusion parameters
  • Intracranial drug delivery
  • Volume of distribution

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Psychiatry and Mental health

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