Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors.

Abstract

BACKGROUND:

Despite aggressive multimodal treatment, survival for patients with glioblastoma remains dismal. One obstacle to improving patient outcomes is the difficulty in delivering adequate therapeutic to the central nervous system due to the presence of the blood-brain barrier. Although direct drug infusion by convection-enhanced delivery (CED) can bypass the blood-brain barrier and facilitate delivery to intracranial tumors, determining the distribution of delivered therapeutic remains problematic. Image guidance is a strategy that can optimize the accuracy of therapeutic delivery.

METHODS:

Here we performed an open-label clinical trial in 10 pet dogs with spontaneous intracranial tumors to examine the target coverage accuracy of delivering polymeric magnetite nanoparticles (PMNPs) encapsulating temozolomide (TMZ). A modified small animal frame was applied to the head of each subject, and PMNPs were delivered stereotactically to the center of the tumor. Magnetic resonance imaging (MRI) was performed immediately postoperatively to examine PMNP distribution, and the animals were followed until death.

RESULTS:

Nine of the 10 dogs underwent PMNP infusion without complications. No infusate backflow was observed during any procedure. In 70% of the cases, the infusion accurately targeted the tumor mass, as determined by the presence of PMNP signal in the tumor on immediate postoperative MRI.

CONCLUSIONS:

These data suggest that CED of PMNPs carrying TMZ is safe in dogs with intracranial tumors and can lead to nanoparticle distribution in the region of the target. Image guidance is an important adjunct to CED, because distribution is unpredictable, with the potential for missed target delivery.

• Authors: Jacob S Young, Giovanna Bernal, Sean P Polster, Luis Nunez, Gustavo F Larsen, Nassir Mansour, Michael Podell, Bakhtiar Yamini
• Journal: World neurosurgery (World Neurosurg) Vol. 117 Pg. e698-e704 (Sep 2018) ISSN: 1878-8769 [Electronic] United States
• PMID: 29960096 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Magnetite Nanoparticles
• Polymers
• Dacarbazine
• Temozolomide

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Brain (diagnostic imaging)
• Convection
• Dacarbazine (administration & dosage, analogs & derivatives)
• Dog Diseases (diagnostic imaging, drug therapy)
• Dogs
• Drug Delivery Systems
• Female
• Glioma (diagnostic imaging, drug therapy, veterinary)
• Magnetic Resonance Imaging
• Magnetite Nanoparticles
• Male
• Nanoparticles
• Pilot Projects
• Polymers
• Supratentorial Neoplasms (diagnostic imaging, drug therapy, veterinary)
• Temozolomide
• Treatment Outcome
• Tumor Burden