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REVIEW ARTICLE

Intracerebral drug delivery using microbubble/nanodroplet-assisted ultrasound to address neurodegenerative diseases

Karen Ea1 ,  Nicolas Taulier2 ,  Christiane Contino-Pépin3 ,  Wladimir Urbach2,4 ,  Stéphane Desgranges3 ,  Hélène Blasco1,5 ,  Yara Al-Ojaimi1 ,  Philippe Corcia1,6 ,  Patrick Vourc’h1,5†* ,  Jean-Michel Escoffre1†*
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1 Université de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, Tours, France
2 Laboratoire d’Imagerie Biomédicale, LIB, Sorbonne Université, CNRS, INSERM, Paris, France
3 Équipe Systèmes Amphiphiles bioactifs et Formulations Eco-compatibles, UPRI, Université d’Avignon, Avignon, France
4 LPENS CNRS UMR 8023 PSL, Paris, France
5 Service de Biochimie et Biologie moléculaire, CHRU de Tours, Tours, France
6 Centre de référence SLA et autres maladies du neurone moteur, CHRU Tours, Tours, France
JCTR, 00061 https://doi.org/10.36922/jctr.24.00061
Submitted: 12 September 2024 | Revised: 18 January 2025 | Accepted: 9 February 2025 | Published: 27 February 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: The blood–brain barrier (BBB) is a selective and semi-permeable barrier essential for protecting the brain’s parenchyma against pathogens and toxic molecules present in the bloodstream. It consists of a monolayer of brain capillary endothelial cells, pericytes, astrocytic end-feet, and neurons. The tight junctions between endothelial cells prevent paracellular transport, further reinforcing its selectivity. However, this high level of selectivity represents a significant challenge for the delivery of therapeutic molecules to the central nervous system. Aim: Microbubble-assisted ultrasound (US) is a promising strategy for transiently permeabilizing the BBB to enable safe, non-invasive, localized, and efficient drug delivery to the brain. This approach enhances drug extravasation and bioavailability. Recently, nanodroplets (NDs) have emerged as good candidates to replace MBs. The aim of this review is to provide an updated overview of the rapidly expanding field of MB/ND-assisted US for the treatment of neurodegenerative diseases. This exciting field bridges research in biology and chemistry (MBs, NDs), US technology and the development of new drugs, small molecules, and biomedicines. The review begins with an update on MBs and NDs and discusses laboratory-manufactured and clinically approved devices such as Sonocloud®, NaviFUS®, and ExAblate Neuro®. It then focuses on the potential use of MB/ND-assisted US in treating neurodegenerative diseases, particularly Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease (HD). Relevance for patients: Acoustically mediated BBB opening is an innovative and rapidly advancing strategy that holds great promise for improving the efficacy of existing treatments for neurodegenerative diseases. It also facilitates the discovery of new therapeutic molecules by enhancing their delivery to the brain.

Graphical abstract
Keywords
Blood–brain barrier opening
Sonoporation
Ultrasound
Microbubbles
Nanodroplets
Neurodegenerative diseases
Funding
We would like to thank the Agence Nationale de la Recherche (ANR) for funding (ANR-22-CE19-0031) and the Région Centre-Val de Loire for the funding of PhD students (K.E.).
Conflict of interest
The authors declare no conflict of interest.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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