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 perfluorocarbon gas microspheres comprising
(1) forming lipid-encapsulated perfluorocarbon gas microspheres by activating a composition comprising (i) a non-aqueous mixture comprising one or more phospholipids selected from DPPA, DPPC and PEG5000-DPPE, in propylene glycol and/or glycerol, and (ii) a perfluorocarbon gas, wherein the non-aqueous mixture comprises equal to or less than 5% w/w (weight/weight) of water, to form lipid-encapsulated perfluorocarbon gas microspheres,
(2) adding an aqueous diluent to the lipid-encapsulated perfluorocarbon gas microspheres, and
(3) administering the lipid-encapsulated perfluorocarbon gas microspheres to a subject.
2. The method of claim 1 , wherein the non-aqueous mixture comprises less than 5% w/w (weight/weight) of water.
3. The method of claim 1 , wherein the composition further comprises a buffer.
4. The method of claim 1 , wherein the composition further comprises a non-phosphate buffer.
5. The method of claim 1 , wherein the one or more phospholipids are present in a concentration of about 0.9 to about 7.5 mg per ml of non-aqueous mixture.
6. The method of claim 1 , wherein the one or more phospholipids are present in a concentration of about 3.75 mg per ml of non-aqueous mixture.
7. The method of claim 1 , wherein the composition comprises less than 5% impurities when stored at room temperature for about 3 months.
8. The method of claim 1 , wherein the perfluorocarbon gas is perfluoropropane gas.
9. The method of claim 1 , wherein PEG5000-DPPE is MPEG5000-DPPE.
10. The method of claim 1 , further comprising adding glycerol and/or propylene glycol to the lipid-encapsulated perfluorocarbon gas microspheres before, during and/or after adding the aqueous diluent.