# Focused ultrasound-mediated disruption of blood plasma protein binding with pharmacological molecules

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $526,888

## Abstract

Project Summary
Region-specific enhancement of drug delivery to the brain, without increasing systemic drug dose or actively
disrupting the blood-brain barrier, has been sought after for effective pharmacological treatment of various
central nervous system disorders. Among different approaches, we propose to enhance the delivery by
unbinding the drug from the plasma proteins to increase the local drug concentration that may be transported
across the vasculature. The overarching goal of our research is to examine the effects of transcranial focused
ultrasound (FUS) on region-specific disruption of plasma protein binding (PPB) with phenytoin (PHT) and to
evaluate if the regional increase of parenchymal PHT uptake results in the suppression of temporal lobe
epilepsy (TLE) in rodents. First, FUS will be noninvasively applied to an ipsilateral hippocampal area of non-
epileptic Sprague-Dawley rats receiving a therapeutic dose of PHT, using varying duty cycles, pulse durations,
and intensities of sonication. The parenchymal PHT uptake will be quantified using anti-PHT
immunohistochemistry, and the FUS parameter that results in the highest uptake level will be identified. Then,
using the parameter, multiple sessions of FUS will be applied to the epileptic brain region of chronic TLE rats
receiving daily therapeutic doses of PHT. Electroencephalography (EEG) will be acquired from the animals
using a wearable wireless EEG device and the frequency/duration of behavioral seizures and epileptographic
EEG will be quantified. These measures will be compared among four combinatorial experimental groups of
FUS(+/-) and PHT(+/-) to examine if the increased delivery of PHT, mediated by FUS, will enhance its anti-
convulsant effects. The animals, both epileptic and non-epileptic, will be evaluated for potential tissue or
vascular damage using histological analysis and for the presence of undesired disruption of the blood-brain
barrier. The proposed method of acoustic disruption of PHT-PPB may provide an elegant and unprecedented
option for suppressing seizure activity associated with focal epilepsy. Similar FUS protocols may also be
applicable to increase regional delivery of a wide range of drugs that have high affinity to plasma proteins.

## Key facts

- **NIH application ID:** 10046533
- **Project number:** 1R21EY031807-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Wonhye Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $526,888
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046533

## Citation

> US National Institutes of Health, RePORTER application 10046533, Focused ultrasound-mediated disruption of blood plasma protein binding with pharmacological molecules (1R21EY031807-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046533. Licensed CC0.

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