TY - JOUR
T1 - Implementation of a chronic unilateral intraparenchymal drug delivery system in a swine model
AU - Kim, Inyong
AU - Paek, Seungleal
AU - Nelson, Brian D.
AU - Knight, Emily J.
AU - Marsh, Michael P.
AU - Bieber, Allan J.
AU - Bennet, Kevin E.
AU - Lee, Kendall H.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/4/30
Y1 - 2014/4/30
N2 - 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.
AB - 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.
KW - Blood brain barrier
KW - Central nervous system
KW - Chronic drug delivery system
KW - Intraparenchymal catheter
KW - Swine model
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U2 - 10.1016/j.jneumeth.2014.01.029
DO - 10.1016/j.jneumeth.2014.01.029
M3 - Article
C2 - 24486877
AN - SCOPUS:84896842607
SN - 0165-0270
VL - 227
SP - 29
EP - 34
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
ER -