Localized Disruption of Blood Albumin–Phenytoin Binding Using Transcranial Focused Ultrasound

Linda Xu, Wonhye Lee, Alexander Rotenberg, Mark Böhlke, Kyungho Yoon, Seung Schik Yoo

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Plasma protein binding (PPB) plays an important role in drug pharmacokinetics, particularly for central nervous system drugs, as PPB affects the blood concentration of unbound drug available to cross the blood–brain barrier (BBB). We report the non-invasive, spatially specific disruption of PPB to phenytoin, an anti-epileptic drug with high affinity to albumin, using 250-kHz focused ultrasound (FUS) delivered in a pulsed manner (55-ms tone burst duration, 4-Hz pulse repetitions). Equilibrium dialysis performed on sonicated phosphate-buffered saline solution containing phenytoin and bovine serum albumin revealed a 27.7% elevation in the unbound phenytoin concentration compared with an unsonicated control. Sonication of a unilateral brain hemisphere in rats (n = 10) after intraperitoneal phenytoin injection revealed increased parenchymal phenytoin uptake compared with the unsonicated hemisphere, without evidence of temperature change or BBB disruption. These findings illustrate the use of FUS as a novel technique for spatially selective disruption of PPB, which may be applied to a wide range of drug–plasma protein interactions.

Original languageEnglish
Pages (from-to)1986-1997
Number of pages12
JournalUltrasound in Medicine and Biology
Volume46
Issue number8
DOIs
Publication statusPublished - 2020 Aug

Bibliographical note

Publisher Copyright:
© 2020 World Federation for Ultrasound in Medicine & Biology

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics

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