Blood-brain barrier opening-based local delivery of 80 nm-sized liposomes in mice using pulsed focused ultrasound

Abstract

Continuous focused ultrasound (FUS) has been mostly used to generate high temperatures necessary for tissue ablation. Pulsed FUS in combination with intravenously injected microbubbles has been shown to open the blood-brain barrier (BBB) to increase plasma-to-tissue permeability, thus presenting a new opportunity for local drug delivery to the targeted part of the brain. We have previously demonstrated a local delivery of doxorubicin to mouse brain tumor tissues by transient BBB opening.[1] However, the next generation of therapeutics is associated with a broader range of clinically meaningful applications. Liposomes are particularly interesting since drug and contrast agent can be combined in a single safe and biodegradable system with a sustained release of content. Therefore, we investigated the brain delivery of fluorescently labeled liposomes by FUS-mediated BBB opening in healthy mice.