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

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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.

ABBREVIATIONS:

BBB, blood-brain barrier

ABBREVIATIONS:

HPLC, high-performance liquid chromatography

ABBREVIATIONS:

LC/ESI-MS/MS, liquid chromatography/electrospray ionization–tandem mass spectrometry/mass spectrometry

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