Microbubbles Containing Lysolipid Enhance Ultrasound‐Mediated Blood–Brain Barrier Breakdown In Vivo

Abstract

Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso‐MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso‐MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso‐MBs or control MBs and gadolinium‐DTPA (Gd‐DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak‐negative pressures 160–480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd‐DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso‐MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid‐shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain.

Bubble-enhanced ultrasonic microfluidic chip for rapid DNA fragmentation

“…Other studies have shown that microbubbles can be used for contrast-enhanced ultrasound imaging. [26][27][28] Ultrasound has already been widely used in microfluidics, for instance for isolating and sorting of microparticles, trapping and lysis of cells and for DNA fragmentation. [29][30][31][32] Huang's group has conducted research on acoustofluidics using trapped microbubbles or microstructure-enhanced ultrasound effects for different applications, such as microfluidic mixing, cell lysis and acoustofluidic pumping.…”

Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and “whole brain” ultrasound

“…Ultrasound exposure to the brain was carried out using a purpose-built setup (Figure 1 B) that allowed reproducible treatment of mice, whilst in an MRI cradle and in a stereotactic frame, and thus, enabling consistent positioning for comparative analysis, as described previously 40 . Briefly, animals were held in position in the cradle using cheek bars for the duration of ultrasound treatment so that the whole brain volume could be consistently exposed.…”

Bridging barriers: advances and challenges in modeling biological barriers and measuring barrier integrity in organ-on-chip systems

“…34 Various approaches to disrupt barrier integrity have been shown to improve movement of therapeutic agents across biological barriers. Such techniques include the use of microbubbles and ultrasound, 35 lasers, 36 microneedles, 37 and nanoparticles. 38…”