Microparticles useful as ultrasonic contrast agents

Abstract

Microparticles are provided comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microparticles contain a gas, liquid or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The microparticles are capable of passing through the capillary systems of a subject.

What is claimed is:  
     
         1 . A composition comprising: 
 a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an outer layer of a cross-linked amphiphilic material and an inner layer of a biodegradable polymer; and    a sugar.    
     
     
         2 . The composition of  claim 1  in which the sugar is sucrose.  
     
     
         3 . The composition of  claim 1  which further comprises a surfactant.  
     
     
         4 . The composition of  claim 3  in which the surfactant is a poloxomer.  
     
     
         5 . The composition of  claim 1  which further comprises a water-soluble polymer.  
     
     
         6 . The composition of  claim 5  in which the water-soluble polymer is a medium molecular weight polyethylene glycol.  
     
     
         7 . The composition of  claim 1  in which the gas is nitrogen.  
     
     
         8 . The composition of  claim 1  in which the biodegradable polymer is selected from the group consisting of polycaprolactone, polylactice, polyglycolide,polylactide-polyglycolide copolymers, copolymers of lactides and lactones, delta-valerolactone, polyalkylcyanoacrylates, polyamides, polyhydroxybutyrates, polydioxanones, poly-beta-aminoketones, polyanhydrides, poly-(ortho)esters, polyglutamic acid, polyaspartic acid and esters of polyglutamic and polyaspartic acids.  
     
     
         9 . The composition of  claim 1  in which the cross-linked amphiphilic material is a cross-linked protein.  
     
     
         10 . The composition of  claim 9  in which the cross-linked protein is cross-linked human serum albumin.  
     
     
         11 . The composition of  claim 1  in which the cross-linked amphiphilic material is cross-linked with glutaraldehyde.  
     
     
         12 . A composition comprising: 
 a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an inner layer of polylactide and an outer layer of glutaraldehyde cross-linked human serum albumin;    glycine; and    polyethylene glycol 3350.    
     
     
         13 . The composition of  claim 12  which is in the form of a dry cake and/or powder.  
     
     
         14 . The composition of  claim 12  which is in the form of an aqueous suspension.