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Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

Yang FY, Lin YL, Chou FI, Lin YC, Hsueh Liu YW, Chang LW, Hsieh YL - PLoS ONE (2014)

Bottom Line: With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater.This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site.Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

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Related in: MedlinePlus

Schematic diagram illustrating the experimental setup for FUS and microdialysis.
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pone-0100104-g003: Schematic diagram illustrating the experimental setup for FUS and microdialysis.

Mentions: To evaluate the variability of BPA concentration within the brain tumor, a commercially available microdialysis probe (MAB 6, Stockholm, Sweden) was applied to sample the unbound BPA in the rat brain. Simultaneously, another microdialysis probe (MAB 7, Stockholm, Sweden) was implanted into the jugular vein toward the rat’s right atrium. For brain ECF sampling, the rat was mounted on a stereotaxic frame. An incision was made in the scalp, and a small hole was drilled on the right side of the skull for implantation of the rigid microdialysis probe in the tumor. After implantation of the microdialysis probes, the probes were perfused with Ringer’s solution (147 mM sodium chloride, 4 mM potassium chloride, 2.2 mM calcium chloride) by a microinjection pump (CMA 402, Stockholm, Sweden) at a flow rate of 2 µL/min. Dialysate samples were collected using a microfraction collector (MAB 85, Stockholm, Sweden). The entire experimental system is shown in Fig. 3.


Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

Yang FY, Lin YL, Chou FI, Lin YC, Hsueh Liu YW, Chang LW, Hsieh YL - PLoS ONE (2014)

Schematic diagram illustrating the experimental setup for FUS and microdialysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061112&req=5

pone-0100104-g003: Schematic diagram illustrating the experimental setup for FUS and microdialysis.
Mentions: To evaluate the variability of BPA concentration within the brain tumor, a commercially available microdialysis probe (MAB 6, Stockholm, Sweden) was applied to sample the unbound BPA in the rat brain. Simultaneously, another microdialysis probe (MAB 7, Stockholm, Sweden) was implanted into the jugular vein toward the rat’s right atrium. For brain ECF sampling, the rat was mounted on a stereotaxic frame. An incision was made in the scalp, and a small hole was drilled on the right side of the skull for implantation of the rigid microdialysis probe in the tumor. After implantation of the microdialysis probes, the probes were perfused with Ringer’s solution (147 mM sodium chloride, 4 mM potassium chloride, 2.2 mM calcium chloride) by a microinjection pump (CMA 402, Stockholm, Sweden) at a flow rate of 2 µL/min. Dialysate samples were collected using a microfraction collector (MAB 85, Stockholm, Sweden). The entire experimental system is shown in Fig. 3.

Bottom Line: With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater.This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site.Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

Show MeSH
Related in: MedlinePlus