Ultrasound targeted microbubble destruction for drug and gene delivery.
BACKGROUND
Gas-filled microbubbles have been used as ultrasound contrast agents for some decades. More recently, such microbubbles have evolved as experimental tools for organ- and tissue-specific drug and gene delivery. When sonified with ultrasound near their resonance frequency, microbubbles oscillate. With higher ultrasound energies, oscillation amplitudes increase, leading to microbubble destruction. This phenomenon can be used to deliver a substance into a target organ, if microbubbles are co-administered loaded with drugs or gene therapy vectors before i.v. injection.


OBJECTIVE
This review focuses on different experimental applications of microbubbles as tools for drug and gene delivery. Different organ systems and different classes of bioactive substances that have been used in previous studies will be discussed.


METHODS
All the available literature was reviewed to highlight the potential of this non-invasive, organ-specific delivery system.


CONCLUSIONS
Ultrasound targeted microbubble destruction has been used in various organ systems and in tumours to successfully deliver drugs, proteins, gene therapy vectors and gene silencing constructs. Many proof of principle studies have demonstrated its potential as a non-invasive delivery tool. However, too few large animal studies and studies with therapeutic aims have been performed to see a clinical application of this technique in the near future. Nevertheless, there is great hope that preclinical large animal studies will confirm the successful results already obtained in small animals.
Mayer
Christian R
CR
University of Heidelberg, Department of Internal Medicine III, Im Neuenheimer Feld 410, 69120 Heidelberg,Germany.
Geis
Nicolas A
NA
Katus
Hugo A
HA
Bekeredjian
Raffi
R
D000818:Animals; D016503:Drug Delivery Systems; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007275:Injections, Intravenous; D045423:Microbubbles / Q000009:adverse effects; D014465:Ultrasonics / Q000009:adverse effects