Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents

Neurosurgery. 2016 May;78(5):726-33. doi: 10.1227/NEU.0000000000001104.

Abstract

Background: Triolein emulsion infusion into the carotid artery has been reported to induce temporary and reversible opening of the blood-brain barrier by increasing vascular permeability.

Objective: To evaluate the effect of triolein emulsion infusion on brain permeance by anticancer agents.

Methods: In the doxorubicin study. 2.4 mg/kg doxorubicin was injected immediately after triolein emulsion (1%, 1.5%, and 2%) infusion into rabbit carotid arteries. Two hours later, bilateral hemispheres and eyeballs were harvested, and doxorubicin concentrations were measured fluorometrically. Doxorubicin ratios of ipsilateral/contralateral hemispheres were compared with those of doxorubicin controls by use of the Kruskal-Wallis test followed by the Dunn test. In the cisplatin study, 10 mg/kg cisplatin was injected immediately after 2% triolein emulsion infusion into rat carotid arteries. Ipsilateral hemispheres were harvested 2, 6, 12, 24, and 36 hours after treatment. Time-dependent cisplatin concentrations were determined by liquid chromatography/electrospray ionization-tandem mass spectrometry/mass spectrometry.

Results: Doxorubicin concentrations were significantly higher in ipsilateral hemispheres and eyeballs in all 3 triolein treatment groups than in doxorubicin controls. In the cisplatin study, cisplatin concentrations in the ipsilateral hemispheres peaked at 6 hours after infusion of cisplatin.

Conclusion: Brain permeance to anticancer agents was increased by triolein emulsion infusion, which suggests that triolein infusion might be a useful adjuvant treatment for brain tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antineoplastic Agents / pharmacokinetics*
  • Blood-Brain Barrier / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Capillary Permeability / drug effects
  • Carotid Arteries*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Emulsions
  • Fluorometry
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Rabbits
  • Triolein / administration & dosage*
  • Triolein / pharmacology*

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Emulsions
  • Triolein
  • Doxorubicin
  • Cisplatin