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


METHODS
Five male pigs underwent 3.0T 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±420mm(3)).


CONCLUSIONS
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.


CONCLUSIONS
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.
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kim.inyong@mayo.edu.
Inyong
I
Kim
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: paek.seungleal@mayo.edu.
Seungleal
S
Paek
Medtronic Neuromodulation, 7000 Central Avenue NE, Mail Stop RCE470, Minneapolis, MN 55432, USA. Electronic address: brian.d.nelson@medtronic.com.
Brian D
BD
Nelson
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: knight.emily@mayo.edu.
Emily J
EJ
Knight
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: marsh.michael@mayo.edu.
Michael P
MP
Marsh
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: bieber.allan@mayo.edu.
Allan J
AJ
Bieber
Division of Engineering, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kbennet@mayo.edu.
Kevin E
KE
Bennet
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: lee.kendall@mayo.edu.
Kendall H
KH
Lee
D000818:Animals; D018481:Convection; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D007839:Functional Laterality; D019786:Gadolinium DTPA / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D015918:Infusion Pumps, Implantable; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013997:Time Factors
D019786:Gadolinium DTPA
Blood brain barrier; Central nervous system; Chronic drug delivery system; Intraparenchymal catheter; Swine model