Ultrasound - Triggered drug delivery with contrast imaging: Effect of microencapsulation method

A method for preparation of hollow, biodegradable polymeric microcapsules for use as contrast agents is described, and strategies for their use in concomitant imaging and drug delivery are outlined. Compared with X-ray or magnetic resonance imaging, diagnostic ultrasound is a safe, relatively inexpensive imaging technique, which allows the physician to view real-time images. Contrast agents are being developed which will greatly enhance the contrast of the received image, when injected into the patients blood stream. We have developed hollow polymeric CA based upon the ability to microencapsulate a solid core of ammonium carbonate which is then removed by decomposition and freeze-drying. The polymer poly DL(lactide-co-glycolide) (PLGA) was chosen for it's FDA approval, and because it has the most rapid in vivo degradation of the alpha-hydroxy acid series. Spray dried and solvent extraction samples were used to test the concept of concomitant drug delivery and imaging. The method of fabrication had an important effect on the drug loading by adsorption, and on the amount of drug that was released when the capsules were insonated with ultrasound in the medical imaging range. Both were greater for spray dried samples. Both frequency and pressure of insonation also influenced 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.