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.
Highlights
The blood-brain barrier (BBB) is a highly specialized endothelial structure occurring along the brain capillaries [1]
The mean peak values were similar to those of the concentration profiles, in which the highest boron accumulation in the brain tumor extracellular fluid (ECF) occurred at 30 min after drug injection and declined rapidly during the elimination phase
BPA has been applied as a potential boron carrier in clinical trials with boron neutron capture therapy (BNCT)
Summary
The blood-brain barrier (BBB) is a highly specialized endothelial structure occurring along the brain capillaries [1]. Several methods have been developed to circumvent this barrier in order to enhance drug delivery into the brain, such as the chemical modification of drugs, the osmotic opening of tight junctions, and the direct injection of the therapeutic agent or agents into the targeted brain area [2]. Recent studies have shown that focused ultrasound (FUS) can enhance the delivery of chemotherapeutic drugs into brain tumors and improve antitumor effects due to FUS-induced BBB disruption [3,4]. As such, imageguided FUS technology may provide a novel strategy for targeted drug delivery in brain tumor treatment [5]. Free drug concentrations cannot be measured if there is interference from signals produced by metabolites
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
