Microbubble oscillations and stability for drug delivery

Abstract

Ultrasound contrast agents have been developed from micron size bubbles whose gas core is enclosed by a polymer, lipid or protein shell. Furthermore, specific designs have been developed for drug delivery in which the ultrasound contrast agent acts as drug delivery vehicle. A drug may be suspended in the shell of these agents which is released at a particular site as the microbubble undergoes destruction. Localized delivery depends on the destruction of a sufficient number of bubbles within a confined geometry typically a capillary or small vessel. Experimental evidence suggests the composition and thickness of the shell play important role in the break-up. Break-up scenarios of buckling have been suggested for elastic shell agents and shape stability for fluid shell agents. However, these have not been rigorously examined theoretically. The formulations of contrast agent designed for drug delivery are highlighted including a description of a double polymeric layer design. Shape stability equations for fluid shell agents are derived and analyzed in limiting cases. Furthermore, biological issues related to potential endothelial cell transport and interactions are briefly discussed.