Ultrasound-Triggered Drug Delivery with Contrast Imaging: Effect of Microencapsulation Method

M.A. Wheatley^1,2, D. El-Sherif¹, R. Shimp^{2  
1}School of Biomedical Science Engineering and Health Systems
²Chemical Engineering
Drexel University
Philadephia, PA  19104
dalia@io.ece.drexel.edu
(215) 895-5831

Medical ultrasound is a highly valuable diagnostic tool, especially when compared with other imaging modalities. It is non-invasive, real-time, portable, extremely safe compared to X-ray, and inexpensive relative to MRI.  Recently, ultrasound contrast agents have been developed which when injected into the body, greatly enhance the
contrast of the acquired image.

We have developed a method for producing hollow microcapsules, with diameters less then 10 microns so they can pass the pulmonary bed after intravenous injection.  We describe the use of these agents for concomitant imaging and drug delivery.  The drug-loaded contrast is imaged as it passes through the region of interest.  At the same time drug release is triggered right at the insonated area.  This study investigates two parameters: The effect of encapsulation method (solvent extraction and spray drying) on the drug payload by adsorption, and the effect of insonation parameters (such as time, insonation frequency and pressure) on the release profile. Hollow polylactide-co-glycolide microcapsules were prepared by the above techniques. The freeze-dried capsules were filtered and sized on a Horiba particle size analyzer.  Zeta potential data was recorded pre- and post drug loading. FITC-BSA was used as a model high molecular weight bioactive drug.  Release studies were performed in vitro in a release chamber fitted with an acoustic window. Insonation
frequencies were in the medical range, at 5 and 10 MHz.  Drug release was measured by an increase in FITC fluorescence in the release medium.  The spray dried sample showed greater adsorption and drug release. The most dramatic increase in release was after 5 minutes for the 10 MHz low (1.25 MPa) pressure insonation, which showed 316% greater release than control, a total of 1.89 mg.