Methods of imaging and delivering therapeutic agents

Abstract

The present disclosure provides imaging agents that are useful for the detection and evaluation of heart conditions, such as myocardial infarction. Upon activation, the imaging agents of the present disclosure may be detected using an ultrasound imaging device.

1 - 24 . (canceled) 
     
     
         25 . A method of preparing a triple emulsion composition, the method comprising:
 (i) emulsifying a first mixture comprising a surfactant, an aqueous phase, and a liquid insoluble in the aqueous phase, to provide a first emulsion;   (ii) emulsifying a second mixture comprising the first emulsion and a second mixture to provide a second emulsion, wherein the second mixture comprises:
 a) a saturated phospholipid, 
 b) an unsaturated phospholipid, and 
 c) an organic solvent, wherein one of the phospholipids (a) and (b) is neutral and the other is charged; and 
   (iii) emulsifying a third mixture comprising the second emulsion and polyvinyl alcohol to provide the triple emulsion composition.   
     
     
         26 . The method of  claim 25 , wherein the insoluble liquid is perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, or a mixture thereof 
     
     
         27 . The method of  claim 25 , wherein the aqueous phase comprises phosphate-buffered saline (PBS). 
     
     
         28 . The method of  claim 25 , wherein the aqueous phase comprises propylene glycol. 
     
     
         29 . The method of  claim 25 , wherein the second mixture further comprises triolein. 
     
     
         30 . The method of  claim 25 , wherein the second mixture further comprises cholesterol. 
     
     
         31 . The method of  claim 25 , wherein the second mixture comprises di stearoylphosphatidylglycerol (DSPG), oleoylphosphatidylcholine (SOPC), triolein and cholesterol. 
     
     
         32 . The method of  claim 25 , wherein the second mixture comprises di stearoylphosphatidylcholine (DSPC), DSPG, SOPC, triolein and cholesterol. 
     
     
         33 . The method of  claim 25 , wherein the third mixture comprises an aqueous polyvinyl alcohol solution, wherein the concentration of polyvinyl alcohol in the aqueous polyvinyl alcohol solution is about 2 wt %. 
     
     
         34 . A method of preparing an imaging agent, the method comprising:
 (i) emulsifying a first mixture comprising a surfactant, water, and a liquid insoluble in water, to provide a first emulsion;   (ii) emulsifying a second mixture comprising the first emulsion and a second mixture to provide a second emulsion, wherein the second mixture comprises:
 a) a saturated phospholipid, 
 b) an unsaturated phospholipid, and 
 c) an organic solvent, wherein one of the phospholipids (a) and (b) is neutral and the other is charged; 
   (iii) emulsifying a third mixture comprising the second emulsion and polyvinyl alcohol to provide the triple emulsion; and   (iv) evaporating the organic solvent from the triple emulsion to provide the imaging agent.   
     
     
         35 . The method of  claim 34 , wherein the insoluble liquid is perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, or a mixture thereof 
     
     
         36 . The method of  claim 34 , wherein the aqueous phase comprises phosphate-buffered saline (PBS). 
     
     
         37 . The method of  claim 34 , wherein the aqueous phase comprises propylene glycol. 
     
     
         38 . The method of  claim 34 , wherein the second mixture further comprises triolein. 
     
     
         39 . The method of  claim 34 , wherein the second mixture further comprises cholesterol. 
     
     
         40 . The method of  claim 34 , wherein the second mixture comprises DSPG, SOPC, triolein and cholesterol. 
     
     
         41 . The method of  claim 34 , wherein the second mixture comprises DSPC, DSPG, SOPC, triolein and cholesterol. 
     
     
         42 . The method of  claim 34 , wherein the third mixture comprises an aqueous polyvinyl alcohol solution, wherein the concentration of polyvinyl alcohol in the aqueous polyvinyl alcohol solution is about 2 wt %. 
     
     
         43 . An imaging agent prepared by a process comprising:
 (i) emulsifying a first mixture comprising a surfactant, water, and a liquid insoluble in water, to provide a first emulsion;   (ii) emulsifying a second mixture comprising the first emulsion, wherein the second mixture comprises:
 (a) a saturated phospholipid, 
 (b) an unsaturated phospholipid, and 
 (c) an organic solvent to provide a second emulsion, wherein one of the phospholipids (a) and (b) is neutral and the other is charged; 
   (iii) emulsifying a third mixture comprising the second emulsion and polyvinyl alcohol (PVA) to provide the triple emulsion; and   (iv) evaporating the organic solvent from the triple emulsion to provide the imaging agent.   
     
     
         44 . The imaging agent of  claim 43 , wherein the insoluble liquid is perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, or a mixture thereof