Implementation of a chronic unilateral intraparenchymal drug delivery system in a swine model

Inyong Kim, Seungleal Paek, Brian D. Nelson, Emily J. Knight, Michael P. Marsh, Allan J. Bieber, Kevin E. Bennet, Kendall H. Lee

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Systemic delivery of pharmacologic agents has led to many significant advances in the treatment of neurologic and psychiatric conditions. However, this approach has several limitations, including difficulty penetrating the blood-brain barrier and enzymatic degradation prior to reaching its intended target. Here, we describe the testing of a system allowing intraparenchymal (IPa) infusion of therapeutic agents directly to the appropriate anatomical targets, in a swine model. New method: Five male pigs underwent 3.0. T magnetic resonance (MR) guided placement of an IPa catheter into the dorso-medial putamen, using a combined system of the Leksell stereotactic arc, a Mayo-developed MRI-compatible pig head frame, and a custom-designed Fred Haer Company (FHC) delivery system. Results: Our results show hemi-lateral coverage of the pig putamen is achievable from a single infusion point and that the volume of the bolus detected in each animal is uniform (1544±420mm3). Comparison with existing method: The IPa infusion system is designed to isolate the intracranial catheter from bodily-induced forces while delivering drugs and molecules into the brain tissue by convection-enhanced delivery, with minimal-to-no catheter track backflow. Conclusion: This study presents an innovative IPa drug delivery system, which includes a sophisticated catheter and implantable pump designed to deliver drugs and various molecules in a precise and controlled manner with limited backflow. It also demonstrates the efficacy of the delivery system, which has the potential to radically impact the treatment of a wide range of neurologic conditions. Lastly, the swine model used here has certain advantages for translation into clinical applications.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalJournal of Neuroscience Methods
Volume227
DOIs
StatePublished - Apr 30 2014

Keywords

  • Blood brain barrier
  • Central nervous system
  • Chronic drug delivery system
  • Intraparenchymal catheter
  • Swine model

ASJC Scopus subject areas

  • Neuroscience(all)

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