Noboru Sasaki
From
In residence at
Imaging, Brain, Neuropsychiatry (iBrain) / INSERM, University of Tours - FR
Host scientist
Jean-Michel Escoffre
PROJECT
Microbubble-assisted ultrasound, a tool for depicting and disrupting blood vessels
Despite the increasing number of drugs and the development of novel-targeted therapies, therapeutic progress remains modest for many prevalent and costly diseases. Major obstacles are the non-specific delivery of drugs and the presence of biologic barriers, including endothelial barriers (e.g., blood-brain barrier). Any targeted and active drug delivery method promoting increased drug bioavailability specifically in diseased tissues, while at the same time minimizing healthy tissue side effects, remains today a major challenge for efficient and safe treatments. Microbubble-assisted ultrasound holds promise for a non-invasive and local drug delivery technology in desired site. Ultrasonically activated microbubbles, employed in medical practice as standard ultrasound contrast agents, transiently increases the vascular permeability and facilitating drug extravasation to the interstitial space and uptake by cells. Although the increase in local extravasation has been reported in various tissues, effects on endothelial barriers of pathological tissues (e.g.,permeability and recovery) and the exact mechanism of the extravasation are controversial. Moreover, the spatial and temporal profiles of the extravasation are obscure. In this context, the aim of this collaboration project is to decipher and explain in-vitro effects of MB-assisted US on the dynamics of endothelial barriers, and the subsequent delivery of molecules with increasing sizes in the surrounding space using 3D cell culture models. This collaborative project provides new scientific insights and a better knowledge of endothelial barrier dynamics, which contribute to increase the effectiveness of drug delivery by MB-assisted US for therapeutic intervention in both human and veterinary clinics.