Formulation of acoustically activatable particles having low vaporization energy and methods for using same

Abstract

Acoustically activatable particles having low vaporization energy and methods for making and using same are disclosed. A particle of material includes a first substance that includes at least one component that is a gas 25° C. and atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure. At least some of the first substance exists in a gaseous phase at the time of encapsulation of the first substance within the second substance to form a bubble. After formation of the bubble, the bubble is condensed into a liquid phase, which causes the bubble to transform into the droplet or emulsion having a core consisting of a liquid. The droplet or emulsion is an activatable phase change agent that remains a droplet having a core consisting of a liquid at 25° C. and atmospheric pressure. The first substance has a boiling point below 25° C. at atmospheric pressure.

What is claimed is: 
     
         1 . A method for medical diagnostic imaging using activatable droplets as contrast agents, the method including:
 producing encapsulated droplets, each encapsulated droplet comprising a liquid encapsulated in a shell, wherein the liquid comprises a liquid phase of a fluorocarbon, a perfluorocarbon, a chlorofluorocarbon, a hydrofluorocarbon, a hydrocarbon, a gas having a boiling point that is below room temperature (25° C.), or combinations thereof;   introducing the encapsulated droplets into a tissue to be imaged;   providing activation energy sufficient to cause the liquid within the encapsulated droplets to change from a liquid phase to a gas phase, causing the encapsulated droplets to increase in size and become bubbles of encapsulated gas; and   performing ultrasonic imaging of the tissue using the bubbles as a contrast agent.   
     
     
         2 . A method for medical therapy using activatable droplets, the method including:
 producing encapsulated droplets, each encapsulated droplet comprising a liquid encapsulated in a shell, wherein the liquid comprises a liquid phase of a fluorocarbon, a perfluorocarbon, a chlorofluorocarbon, a hydrofluorocarbon, a hydrocarbon, a gas having a boiling point that is below room temperature (25° C.), or combinations thereof;   delivering the encapsulated droplets to a target region; and providing activation energy sufficient to cause the liquid within the encapsulated droplets to change from a liquid phase to a gas phase,   causing the encapsulated droplets to increase in size and become bubbles of encapsulated gas, wherein the bubbles obstruct the flow of blood, oxygen, or nutrients to cells within the target region.   
     
     
         3 . The method of  claim 2  wherein the target region includes a tumor, cancerous cells, or pre-cancerous cells. 
     
     
         4 . A method of size selection of particles, comprising:
 exposing droplets or emulsions having at least one component that is a gas at room temperature and atmospheric pressure encapsulated in liquid form inside a lipid, protein, or polymer capsule particles to at least one of a pressure other than atmospheric pressure and a temperature other than room temperature, thereby causing some portion of the particle distribution to become activated; and   separating the activated particles from the non-activated particles.