The Role of Ultrasound-Driven Microbubble Dynamics in Drug Delivery: From Microbubble Fundamentals to Clinical Translation

Abstract

In the last couple of decades, ultrasound-driven microbubbles have proven excellent candidates for local drug delivery applications. Besides being useful drug carriers, microbubbles have demonstrated the ability to enhance cell and tissue permeability and as a consequence, drug uptake herein. Notwithstanding the large amount of evidence for their therapeutic efficacy, open issues remain. Due to the vast amount of ultrasound-and microbubble-related parameters that can be altered, and the variability in different models, the translation from basic research to (pre-)clinical studies has been hindered. This review aims at connecting the knowledge gained from fundamental microbubble studies to the therapeutic efficacy seen in in vitro and in vivo studies, with an emphasis on a better understanding of the response of a microbubble upon exposure to ultrasound and its interaction with cells and tissues. More specifically, we address the acoustic settings and microbubble-related parameters i.e. bubble size and physico-chemistry of the bubble shell that play a key role in microbubble-cell interactions and in the associated therapeutic outcome. Additionally, new techniques that may provide additional control over the treatment, such as monodisperse microbubble formulations, tunable ultrasound scanners and cavitation detection techniques, are discussed. An in-depth understanding of the aspects presented in this work could eventually lead the way to more efficient and tailored microbubble-assisted ultrasound therapy in the future.

Nonlinear power loss in the oscillations of coated and uncoated bubbles: Role of thermal, radiation and encapsulating shell damping at various excitation pressures

“…For the stable non-destructive bubble oscillations Rmax R 0 , STDR is higher than P Df r and SuHf r even when SH oscillations occur. Coated bubbles are used as ultrasound contrast agents (UCAs) in ultrasound imaging [11][12][13]40,45,[65][66][67][68] where higher scattering and small attenuation are desired. The scattering defines the ability of UCA to enhance the echogenicity of the target.…”

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

“…In contrast-enhanced ultrasound imaging the blood pool is infused with lipid-shelled micron-sized gas bubbles, named microbubbles, which respond to ultrasound by cavitating, i.e. expanding and contracting along with the pressure phases of the ultrasound wave [15][16][17] . The strong echo arising from cavitation makes microbubbles excellent contrast agents for imaging.…”

Preclinical Ultrasound Imaging—A Review of Techniques and Imaging Applications

“…These microbubbles can be formulated to be used not only as contrast-enhancing agents but also as theranostic agents since targeting ligands can be relatively easily attached to the lipid shells and a drug payload incorporated within or loaded onto the microbubble shells. Although it is known that the drug payload can be released by insonation of the contrast microbubble by a high pressure acoustic pulse the translation of results obtained under highly controlled conditions in vitro have not yet been effectively translated to preclinical and clinical studies [34]. However, the development of mono-disperse microbubbles coupled with increasing access to the drive electronics within commercial preclinical scanners is likely to prompt new imaging sequences specifically tailored to these unique microbubble formulations and provide new and exciting theranostic applications.…”