Nucleation, mapping and control of cavitation for drug delivery

Acoustically driven bubbles produce a range of mechanical, thermal and chemical effects that can be exploited in drug delivery applications. Significant improvements in the targeting, distribution and efficacy of both current and emerging therapeutics can be achieved, from small molecules to biologics and nucleic-acid-based drugs. This Review describes how specially designed cavitation nuclei in the form of solid, liquid or gas particles can enable the triggered release of drugs, promote the permeabiliziation of challenging biological barriers and enhance drug delivery through tissue regions where diffusion alone is inadequate. Scalable strategies for mapping and controlling cavitation activity to harness its therapeutic potential at depth within the body are discussed, alongside current and emerging applications for the treatment of diseases, including cancer and stroke. This Review describes how acoustic cavitation can be used to improve the delivery of drugs for the treatment of diseases such as cancer and stroke. Methods for seeding cavitation, treatment monitoring, and current and future clinical applications are described. Key pointsA major challenge in the treatment of diseases such as cancer and stroke is achieving a sufficient concentration of a drug throughout the target region without producing toxic side effects elsewhere in the body.Oscillating microbubbles driven by ultrasound produce a range of mechanical, thermal and chemical effects that can be used to enable both localized delivery and improved distribution of drugs in tissue.This approach can be used to deliver both conventional small-molecule drugs and more recent biological therapeutics to areas of the body that are normally inaccessible, including across the blood-brain barrier and into solid tumours.Ultrasound-responsive microparticles and nanoparticles can either be used as drug carriers or co-administered with a free drug into the bloodstream, providing cavitation nuclei that reduce the ultrasound pressures required to achieve effective drug delivery.The production of strong acoustic emissions during cavitation-enhanced delivery enables acoustic localization and mapping of bubble activity in real time for treatment monitoring.