Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices

Khalil B. Ramadi, Ashvin Bashyam, Chris J. Frangieh, Erin B. Rousseau, Max J. Cotler, Robert Langer, Ann M. Graybiel, Michael J. Cima

    Research output: Contribution to journalArticle

    Abstract

    Treatments for neurologic diseases are often limited in efficacy due to poor spatial and temporal control over their delivery. Intracerebral delivery partially overcomes this by directly infusing therapeutics to the brain. Brain structures, however, are nonuniform and irregularly shaped, precluding complete target coverage by a single bolus without significant off-target effects and possible toxicity. Nearly complete coverage is crucial for effective modulation of these structures. We present a framework with computational mapping algorithms for neural drug delivery (COMMAND) to guide multi-bolus targeting of brain structures that maximizes coverage and minimizes off-target leakage. Custom-fabricated chronic neural implants leverage rational fluidic design to achieve multi-bolus delivery in rodents through a single infusion of radioactive tracer (Cu-64). The resulting spatial distributions replicate computed spatial coverage with 5% error in vivo, as detected by positron emission tomography. COMMAND potentially enables accurate, efficacious targeting of discrete brain regions. Ramadi et al. combine computational algorithms and rational fluidic design to develop a framework to maximize coverage of brain structures in intracerebral infusions while minimizing off-target leakage.

    Original languageEnglish (US)
    Article number107734
    JournalCell Reports
    Volume31
    Issue number10
    DOIs
    StatePublished - Jun 9 2020

    Keywords

    • brain
    • computational method/algorithm
    • drug delivery
    • intracerebral infusion
    • microdevice
    • microprobe

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Ramadi, K. B., Bashyam, A., Frangieh, C. J., Rousseau, E. B., Cotler, M. J., Langer, R., Graybiel, A. M., & Cima, M. J. (2020). Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices. Cell Reports, 31(10), [107734]. https://doi.org/10.1016/j.celrep.2020.107734