Microbubble-mediated ultrasound drug-delivery and therapeutic monitoring

ABSTRACT

Introduction: 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.

KEYWORDS:

• Contrast agents
• diagnostic imaging
• drug-delivery
• microbubbles
• sonoporation
• therapeutic monitoring
• ultrasound

Article highlights

• Ultrasound contrast agents (UCAs), used in conjunction with ultrasound can play a major role in clinical decision-making.

• Recent advances in the design of UCAs have opened up powerful microbubble applications such as ultrasound molecular imaging, site-specific drug delivery and triggered-release of therapeutic payloads.

• In addition to their exploitation for diagnosis, ultrasound (US) combined with UCAs today represent a new method of localised drug delivery, in which sonoporation induces a transient opening of biological barriers ultimately leading to the uptake and enhanced accumulation of drugs in the targeted region.

• Drug-delivery using contrast-enhanced ultrasound (CEUS) has the potential of becoming a clinically accepted approach for locally potentiating anticancer chemotherapies; and an effective adjunct with recombinant tissue plasminogen activator (rt-PA) for clot lysis.

• Careful evaluation of the choice of drugs, clinical indication, ultrasound settings, microbubble type and concentration is needed to facilitate translation of sonoporation to the clinic.

• Ultimately, the overall goal of imaging, drug-delivery and monitoring response to treatment by using the same equipment would be the perfect drug delivery system, combining as it does: ease-of-use, mobility, real-time and bedside availability.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.