Alexander L. Klibanov PhD, Presenter: Research Grant, Koninklijke Philips NV Co-founder, Targeson, Inc Stockholder, Targeson, Inc Institutional research collaboration, AstraZeneca PLC

1) To identify the basic principles of ultrasound energy deposition as applied to molecular imaging and image-guided therapeutic interventions. 2) To combine the general physical principles of ultrasound-microbubble interaction, drug-carrier systems pharmacokinetics and ultrasound contrast imaging, apply this knowledge for the development of triggered delivery approaches in the setting of personalized medicine. 3) To understand advantages and disadvantages of ultrasound application in the potential image-guided intervention designs. 4) To identify and compare potential clinical applications of ultrasound-guided drug delivery.

The reason of ultrasound use in drug delivery is to enhance drug action specifically in the area of disease. The design of such therapeutic intervention should assure that drug deposition or action enhancement take place only in the disease site, with the general goal to improve the therapeutic index. There are several approaches to ultrasound-assisted drug delivery. The first approach, closest to clinical practice, takes advantage of existing ultrasound contrast agents (intravenous gas microbubbles approved in US for cardiac imaging). When these bubbles are co-injected intravenously with the drugs, and ultrasound energy applied to the areas of disease, localized energy deposition leads to endothelium activation or transient "softening" of blood brain barrier (BBB). Drugs (including antibodies or liposomes) can thus transit BBB and achieve therapeutic action. Ultrasound imaging can be used for targeted focusing of ultrasound energy in the areas of disease. Second approach suggests attaching microbubbles to the drug or a drug carrier (including nucleic acid drugs). Microbubbles can be complexed with drug or gene carrier nanoparticles, so that local action of ultrasound would result in triggered drug release/deposit or transfection in the ultrasound-treated area. Third approach involves targeted microbubble design, as in ultrasound molecular imaging. Combination of targeted microbubbles with drug carrier makes possible unfocused ultrasound use, to act only in the areas of the target receptor expression, where microbubbles adhere and ultrasound energy is then deposited. Lately, formulation moved from microbubbles to smaller nanodroplet drug carriers, to reach interstitium, where drug release could take place upon ultrasound treatment. Overall, combination of ultrasound imaging, including contrast (molecular) imaging, focused ultrasound, and drug carrier systems will lead to novel image-guided therapies, especially applicable in the era of personalized medicine.

Klibanov, A, Sonographically-guided Drug Therapy.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/13011421.html