Microbubble-mediated ultrasound drug-delivery and therapeutic monitoring

Abstract

Recent developments in ultrasound imaging and ultrasound contrast agents (UCAs) improved diagnostic confidence in echography and set into motion their combined use as a tool for drug delivery and therapeutic monitoring. Non-invasive, precise and targeted delivery of drug molecules to pathological tissues by employing different mechanisms of drug release is becoming feasible. Areas covered: We sought to describe: the nature and features of UCAs; outline current contrast-specific imaging modes; before describing a variety of strategies for using ultrasound and microbubbles as a drug delivery system. Our expert opinion focusses on results and prospects of using ultrasound and microbubbles as a dual modality for drug delivery and therapeutic monitoring. Expert opinion: Today, ultrasound and microbubbles present a realistic prospect as drug delivery tools that have been demonstrated in a variety of animal models and clinical indications. Besides delivering drugs, ultrasound and microbubbles have demonstrated added value through therapeutic monitoring and assessment. Successful evaluation of the sonoporation mechanism(s), ultrasound parameters, drug type and dose will need to be addressed before translating this technology for clinic use. Ultimately, the development of a strategy for monitoring targeted delivery and its implementation in clinical practice would advance therapeutic treatment to a new qualitative level.

Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model

“…Ultrasound contrast agents (UCAs) are microbubbles consisting of a gaseous core surrounded by a biocompatible shell. UCAs are currently used for diagnostic medical ultrasounds (Sennoga et al, 2017).…”

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

“…Lastly, a completely separate and additional advantage of such LCM/ND lipid nanoemulsion(s), as a component of this combination therapeutic, stems from the characteristic lipid-coated microbubble subpopulation (D'Arrigo 2011) existing in this nanoemulsion type. Specifically, such preformed (lipidstabilized) microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment Alonso et al 2010;Alonso et al 2011;Aslund et al 2017;Bing et al 2014;D'Arrigo 2015;Delalande et al 2013;Goliaei et al 2015;Kotopoulis et al 2013;Kotopoulis et al 2014;Lammers et al 2015;Marquet et al 2011 O' Reilly et al 2017;Paefgen et al 2015;Qin et al 2016;Sennoga et al 2016), if additionally desired for the Alzheimer's patient.…”

Targeted enhancement of flotillin-dependent endocytosis augments cellular uptake and impact of cytotoxic drugs

“…Most experimental strategies that assess the ability of USMB to enhance drug uptake and efficacy involve pre-treatment of cells with the drug in question, and then ongoing incubation in this drug solution following USMB stimulation. Hence, these strategies do not distinguish between access of drugs to the cellular interior through transient pores that form and re-seal during or immediately after USMB (<1 min), or the sustained enhancement of fluid-phase endocytosis as we 48 and others [44][45][46][47] have observed.…”

“…USMB treatment elicits the formation of transient pores in the plasma membrane 44 . An emerging additional outcome of USMB treatment is an increase in the rate of endocytosis [44][45][46][47] .…”