# Image-guided focused ultrasound-mediated intranasal brain drug delivery technique (FUSIN)

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $410,465

## Abstract

PROJECT SUMMARY/ABSTRACT
More than 50 million Americans are affected by neurological diseases each year, with a cost of more than $650
billion. Despite the high prevalence and substantial economic burden, the present outlook for patients suffering
from many types of brain diseases remains poor due to the failure of conventional therapies. Treatment of brain
diseases is challenging because invasive surgeries can damage healthy brain tissue, the blood-brain barrier
(BBB) blocks most systemically administered drugs from entering the brain, and
many therapeutic agents with
beneficial effects in the brain have adverse side effects in other organs and tissues. The currently available
techniques for brain drug delivery are invasive (e.g., convection-enhanced delivery), lack specific targeting to
the diseased site (e.g., intranasal brain drug delivery), or are associated with systemic toxicity [e.g., focused
ultrasound (FUS)-induced BBB disruption (FUS-BBBD) for the delivery of drugs injected into the systemic
circulatory system]. The objective of this proposal is to develop f ocused ultrasound combined with
microbubble-mediated intranasal delivery (FUSIN), which will achieve noninvasive and spatially targeted
delivery of therapeutic agents to diseased brain sites without jeopardizing healthy regions of the brain
and other organs. FUSIN utilizes the intranasal route for direct nose-to-brain drug administration, thereby
bypassing the BBB and minimizing systemic exposure. It uses focused ultrasound to induce microbubble
cavitation (expansion and contraction of microbubbles) within the focal zone of the FUS beam, leading to
enhanced drug delivery at the FUS-targeted brain location. Our objective will be achieved by completing the
following three specific aims using gold nanoparticles (AuNPs) as model agents and a mouse model of diffuse
intrinsic pontine glioma, the deadliest cancer in children, as a model disease. Aim 1 will identify the biophysical
mechanisms of FUSIN-mediated agent transport using in vivo two-photon microscopy. Aim 2 will systematically
evaluate FUSIN delivery efficiency and effect on normal tissue to assess its potential as a platform technology
for brain drug delivery. Aim 3 will assess the feasibility and safety of real-time passive cavitation imaging-guided
FUSIN to control AuNP delivery location and concentration through cavitation dose painting. The proposed
research contains three main innovations: (1) the microbubble pump effect is proposed as a novel
mechanism for microbubble-mediated drug delivery; (2) FUSIN is a novel spatially targeted brain drug delivery
technique; and (3) cavitation dose painting is a novel approach for controlled drug delivery. This project is
significant because FUSIN has the potential to impact the clinical management of a broad spectrum of
brain disorders by significantly enhancing therapeutic agent delivery to diseased brain sites,
substantially reducing toxicity to healthy brain regions and other organ...

## Key facts

- **NIH application ID:** 9869898
- **Project number:** 5R01EB027223-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hong Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,465
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869898

## Citation

> US National Institutes of Health, RePORTER application 9869898, Image-guided focused ultrasound-mediated intranasal brain drug delivery technique (FUSIN) (5R01EB027223-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869898. Licensed CC0.

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