Page 7 - JCTR-11-2

Journal of Clinical and

Translational Research

REVIEW ARTICLE
Intracerebral drug delivery using

microbubble/nanodroplet-assisted ultrasound
to address neurodegenerative diseases

Karen Ea 1 , Nicolas Taulier 2 , Christiane Contino-Pépin 3 ,
Wladimir Urbach 2,4 , Stéphane Desgranges 3 , Hélène Blasco 1,5 ,
Yara Al-Ojaimi 1 , Philippe Corcia 1,6 , Patrick Vourc’h 1,5† * ,
and Jean-Michel Escoffre *
1†
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
† These authors contributed equally 4 LPENS CNRS UMR 8023 PSL, Paris, France
to this work. 5 Service de Biochimie et Biologie moléculaire, CHRU de Tours, Tours, France
*Corresponding authors: 6 Centre de référence SLA et autres maladies du neurone moteur, CHRU Tours, Tours, France
Patrick Vourc’h
(patrick.vourch@univ-tours.fr)
Jean-Michel Escoffre
(jean-michel.escoffre@inserm.fr)
Citation: Ea K, Taulier N, Abstract
Contino-Pépin C, et al.
Intracerebral drug delivery Background: The blood–brain barrier (BBB) is a selective and semi-permeable barrier
using microbubble/nanodroplet- essential for protecting the brain’s parenchyma against pathogens and toxic molecules
assisted ultrasound to address present in the bloodstream. It consists of a monolayer of brain capillary endothelial
neurodegenerative diseases.
J Clin Transl Res. 2025;11(2):1-27. cells, pericytes, astrocytic end-feet, and neurons. The tight junctions between
doi: 10.36922/jctr.24.00061 endothelial cells prevent paracellular transport, further reinforcing its selectivity.
Received: September 12, 2024 However, this high level of selectivity represents a significant challenge for the
delivery of therapeutic molecules to the central nervous system. Aim: Microbubble-
1st revised: November 26, 2024 assisted ultrasound (US) is a promising strategy for transiently permeabilizing the BBB
2nd revised: December 8, 2024 to enable safe, non-invasive, localized, and efficient drug delivery to the brain. This
3rd revised: January 8, 2025 approach enhances drug extravasation and bioavailability. Recently, nanodroplets
(NDs) have emerged as good candidates to replace MBs. The aim of this review is to
4th revised: January 18, 2025 provide an updated overview of the rapidly expanding field of MB/ND-assisted US for
Accepted: February 9, 2025 the treatment of neurodegenerative diseases. This exciting field bridges research in
Published online: February 27, biology and chemistry (MBs, NDs), US technology and the development of new drugs,
2025 small molecules, and biomedicines. The review begins with an update on MBs and
NDs and discusses laboratory-manufactured and clinically approved devices such as
Copyright: © 2025 Author(s).
®
®
®
This is an open-access article Sonocloud , NaviFUS , and ExAblate Neuro . It then focuses on the potential use of
distributed under the terms of the MB/ND-assisted US in treating neurodegenerative diseases, particularly Alzheimer’s
Creative Commons AttributionNon- disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease
Commercial 4.0 International (CC
BY-NC 4.0), which permits all (HD). Relevance for patients: Acoustically mediated BBB opening is an innovative
non-commercial use, distribution, and rapidly advancing strategy that holds great promise for improving the efficacy of
and reproduction in any medium, existing treatments for neurodegenerative diseases. It also facilitates the discovery of
provided the original work is
properly cited. new therapeutic molecules by enhancing their delivery to the brain.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Blood–brain barrier opening; Sonoporation; Ultrasound; Microbubbles;
regard to jurisdictional claims in
published maps and institutional Nanodroplets; Neurodegenerative diseases
affiliations.

Volume 11 Issue 2 (2025) 1 doi: 10.36922/jctr.24.00061