Controlled release of dopamine from a polymeric brain implant: In vivo characterization

Authors

  • Matthew J. During MD, FRACP,

    1. Department of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, CT
    2. Department of Neurology, Massachusetts General Hospital, Boston, MA
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  • Mr. Andrew Freese BA,

    1. Division of Health Sciences and Technology Massachusetts Intitute of Technology, Cambridge, MA
    2. Whitaker College of Health Sciences, Technology and Management, Massachusetts Intitute of Technology, Cambridge, MA
    Current affiliation:
    1. Department of Neurology, Massachusetts General Hospital, Boston, MA
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  • Bernhard A. Sabel PhD,

    1. Department of Brain and Cognitive Sciences, Massachusetts Intitute of Technology, Cambridge, MA
    2. Institute of Medical Psychology, University of Munich School of Medicine, Munich, FRG
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  • Dr. W. Mark Saltzman PhD,

    1. Division of Health Sciences and Technology Massachusetts Intitute of Technology, Cambridge, MA
    2. Whitaker College of Health Sciences, Technology and Management, Massachusetts Intitute of Technology, Cambridge, MA
    3. Department of Chemical Engineering, Massachusetts Intitute of Technology, Cambridge, MA
    Current affiliation:
    1. Department of Chemical Engineering, Johns Hopkins University, Baltimore, MD
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  • Ariel Deutch PhD,

    1. Department of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, CT
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  • Robert H. Roth PhD,

    1. Department of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, CT
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  • Dr. Robert Langer ScD

    Corresponding author
    1. Division of Health Sciences and Technology Massachusetts Intitute of Technology, Cambridge, MA
    2. Whitaker College of Health Sciences, Technology and Management, Massachusetts Intitute of Technology, Cambridge, MA
    3. Department of Chemical Engineering, Massachusetts Intitute of Technology, Cambridge, MA
    • E25-342, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139
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Abstract

Intracerebral microdialysis was used to evaluate the long-term in vivo release of dopamine from ethylene-vinyl acetate (EV Ac)-dopamine copolymer matrix discs for up to 65 days following striatal implantation. Dopamine release occurred through a single cavity present on one side of the disc, which was otherwise fully coated with an additional, impermeable layer of EV Ac. At 20 days following implantation of the device, extracellular concentrations of dopamine within the striatum reached micromolar levels, over 200-fold greater than control values. Release of dopamine was shown to be stable and maintained for the 2-month duration of the experiment. Histological examination confirmed the biocompatible nature of the implant. There are potential applications of this technology to the treatment of Parkinson's disease and other neurological and psychiatric disorders.

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