Lipid-encapsulated gas microsphere compositions and related methods
The invention provides, inter alia, improved lipid formulations used to generate lipid-encapsulated gas microspheres, and methods of their use.
1. A method of using lipid-encapsulated perfluoropropane gas microspheres for ultrasound contrast imaging comprising
(1) forming lipid-encapsulated perfluoropropane gas microspheres by
(a) forming a combined mixture by adding an aqueous diluent to a composition comprising a non-aqueous mixture in contact with a perfluoropropane gas, said non-aqueous mixture having less than 5% w/w (weight/weight) of water, and comprising DPPA, DPPC and MPEG-5000-DPPE in a ratio of about 10:82:8 (mole %), in propylene glycol and/or glycerol, and
(b) activating the combined mixture to form lipid-encapsulated perfluoropropane gas microspheres,
(2) administering the lipid-encapsulated perfluoropropane gas microspheres to a subject, and
(3) obtaining an ultrasound image of the subject.
2. The method of claim 1 , wherein the non-aqueous mixture has a lipid concentration of about 0.1 to about 10 mg per ml.
3. The method of claim 1 , wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, propylene glycol, and glycerol.
4. The method of claim 3 , wherein the weight ratio of DPPA, DPPC and MPEG5000-DPPE combined to propylene glycol to glycerol is in a range of about 1:100:100 to about 1:600:700.
5. The method of claim 1 , wherein the lipid-encapsulated perfluoropropane gas microspheres have an average diameter ranging from about 1.0 microns to about 2.0 microns.
6. The method of claim 5 , wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10 8 /mL after activation.
7. The method of claim 1 , wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10 8 /mL after activation.
8. The method of claim 1 , wherein activating the combined mixture comprises agitating the combined mixture for 20-45 seconds.
9. The method of claim 1 , wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, and propylene glycol.
10. The method of claim 9 , wherein the weight ratio of DPPA, DPPC and MPEG5000-DPPE, combined, to propylene glycol is in a range of about 1:100 to about 1:600.
11. A method of using lipid-encapsulated perfluoropropane gas microspheres for ultrasound contrast imaging comprising
(1) forming lipid-encapsulated perfluoropropane gas microspheres by activating a composition comprising a non-aqueous mixture in contact with a perfluoropropane gas, said non-aqueous mixture having less than 5% w/w (weight/weight) water, and comprising DPPA, DPPC and MPEG5000-DPPE in a ratio of about 10:82:8 (mole %) in propylene glycol and/or glycerol,
(2) administering the lipid-encapsulated perfluoropropane gas microspheres to a subject, and
(3) obtaining an ultrasound image of the subject.
12. The method of claim 11 , wherein the non-aqueous mixture has a lipid concentration of about 0.1 to about 10 mg per ml.
13. The method of claim 12 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).
14. The method of claim 11 , wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, propylene glycol, and glycerol.
15. The method of claim 14 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).
16. The method of claim 11 , wherein the lipid-encapsulated perfluoropropane gas microspheres have an average diameter ranging from about 1.0 microns to about 2.0 microns.
17. The method of claim 16 , wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10 8 /mL after activation.
18. The method of claim 17 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).
19. The method of claim 16 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).
20. The method of claim 11 , wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10 8 /mL after activation.
21. The method of claim 20 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).
22. The method of claim 11 , wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).