Driving delivery vehicles with ultrasound

doi:10.1016/j.addr.2008.03.002

Advanced Drug Delivery Reviews

Volume 60, Issue 10, 30 June 2008, Pages 1097-1102

https://doi.org/10.1016/j.addr.2008.03.002 Get rights and content

Abstract

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled “Ultrasound for Drug and Gene Delivery,” addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized.

Section snippets

Mechanisms

Historically, the scattered waves resulting from regions of varied tissue density and compressibility have provided the basis for ultrasound images. More recently, the tiny displacements of tissues by the propagating wave have also been utilized to image local tissue properties [3], [4]. These same displacements result in secondary effects that can be harnessed for therapeutic benefit. With each ultrasonic cycle, a fraction of the energy in the propagating wave is absorbed by tissue, resulting

Vehicles

The use of vehicles that are activated by the thermal or mechanical properties of ultrasound and the co-administration of drugs that passively accumulate in regions affected by ultrasound are discussed below. Major classes of vehicles activated by ultrasound include microbubbles, micelles and liposomes, and perfluorocarbon nanoparticles.

Early studies involved the systemic co-injection of a particle or imaging probe together with a microbubble, followed by local insonation to activate the

Applications

The following reviews describe many of the important applications of ultrasound-enhanced drug delivery, including transdermal delivery, delivery to solid tumors, delivery across the blood brain barrier, and enhanced thrombolysis. Transdermal delivery is perhaps the most widely recognized application of ultrasonically-enhanced drug delivery based on the approval of the Sontra Medical (Echo Therapeutics, Inc) system for transdermal delivery of topical therapeutics in 2004 [42]. Other

Other issues

While limited applications of ultrasonic drug and gene delivery have been approved for human use, other applications may be hastened by auxiliary developments. Many endothelial cell surface receptors have recently been identified — and these are accessible to the nano-and micron-sized particles frequently employed in ultrasound delivery systems [48], [49], [50]. These accessible receptors greatly expand the opportunities and methodologies to be considered in ultrasound-enhanced delivery.

Conclusion

In summary, the many mechanisms by which ultrasound can enhance the efficacy of drugs and genes and alter drug delivery vehicles are currently areas of intense study, with several promising clinical applications. The design of ultrasound systems, correlative imaging systems, and drug delivery vehicles each engineered to capitalize on the known mechanisms is well underway. Many challenges remain to be solved in optimizing these techniques, but there is great excitement and enthusiasm generated

Acknowledgements

I would like to thank the many wonderful colleagues and collaborators who have been a part of the work in my own laboratory over the past 20 years as well as the support of NIH CA 103828 in fostering ultrasound-enhanced drug delivery.

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^☆: This commentary is part of the Advanced Drug Delivery Reviews theme issue on “Ultrasound in Drug and Gene Delivery”.

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CommentaryDriving delivery vehicles with ultrasound☆

Abstract

Section snippets

Mechanisms

Vehicles

Applications

Other issues

Conclusion

Acknowledgements

Ultrasound in Medicine and Biology

Ultrasound in Medicine and Biology

Lancet

Ultrasound In Medicine And Biology

Journal Of The American College Of Cardiology

Ultrasound Med Biol

Journal of Controlled Release

Ultrasonics Sonochemistry

Thrombosis Research

Biochimica Et Biophysica Acta-Biomembranes

Ultrasound in Medicine and Biology

Journal of Controlled Release

Ultrasound in Medicine and Biology

Ultrasound In Medicine And Biology

Ultrasound in Medicine & Biology

Colloids and Surfaces B-Biointerfaces

Advanced Drug Delivery Reviews

Trends in Cardiovascular Medicine

Nuclear Medicine and Biology

Biomaterials

Journal of the American College of Cardiology

Biomaterials

Stimulation of tissue regeneration by means of ultrasound

Clinical Science

Healing sound: the use of ultrasound in drug delivery and other therapeutic applications

Naturalist Review Drug Discoveries

Membrane disruption by optically controlled microbubble cavitation

Nature Physics

Ultrasound-induced cell lysis and sonoporation enhanced by contrast agents

Journal of the Acoustical Society of America

Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound

Circulation

Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue

Circulation

Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model

Radiology

Direct observations of ultrasound microbubble contrast agent interaction with the microvessel wall

Journal of the Acoustical Society of America

Commentary
Driving delivery vehicles with ultrasound☆