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

Jacob S. Young, Giovanna Bernal, Sean P. Polster, Luis Nunez, Gustavo Larsen, Nassir Mansour, Michael Podell, Bakhtiar Yamini

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e698-e704
JournalWorld Neurosurgery
Volume117
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

Fingerprint

Magnetite Nanoparticles
Supratentorial Neoplasms
Convection
Nanoparticles
Canidae
temozolomide
Drug Therapy
Neoplasms
Dogs
Magnetic Resonance Imaging
Combined Modality Therapy
Pets
Glioblastoma
Therapeutics
Central Nervous System
Head
Clinical Trials
Survival

Keywords

  • Canine
  • Convection enhanced delivery
  • Glioma
  • Nanoparticles
  • Stereotactic
  • Temozolomide

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors. / Young, Jacob S.; Bernal, Giovanna; Polster, Sean P.; Nunez, Luis; Larsen, Gustavo; Mansour, Nassir; Podell, Michael; Yamini, Bakhtiar.

In: World Neurosurgery, Vol. 117, 01.09.2018, p. e698-e704.

Research output: Contribution to journalArticle

Young, Jacob S. ; Bernal, Giovanna ; Polster, Sean P. ; Nunez, Luis ; Larsen, Gustavo ; Mansour, Nassir ; Podell, Michael ; Yamini, Bakhtiar. / Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors. In: World Neurosurgery. 2018 ; Vol. 117. pp. e698-e704.
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AB - 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.

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