High-concentration liposome processing method
First Claim
1. A method of preparing a suspension of liposomes having a lipid concentration of greater than about 300 μ
- m/ml, and liposomes sizes no greater than about 0.4 microns, said method comprisingdissolving liposomes-forming lipids in a chlorofluorocarbon solvent, to form a lipid-in-solvent solution,injecting the lipid solution, in liquid form, into an aqueous medium, under pressure and temperature conditions at which lipid frothing is largely prevented, and at an injection rate that produces predominantly oligolamellar liposomes,during said injecting, removing injected chlorofluorocarbon solvent from the aqueous medium at substantially the same rate that it is introduced into the medium,also during said injecting, extruding liposomes formed in the aqueous medium to reduce the sizes of the largest liposomes to less than about 0.4 microns, andcontinuing said injecting, removing and extruding until the lipid concentration in the aqueous medium is at least about 300 μ
m/ml.
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Abstract
A method of preparing a concentrated liposome suspension having a lipid concentration of greater than about 250 μm/ml and liposome sizes no greater than about 0.4 microns. A solution of vesicle-forming lipids in a chlorofluorocarbon solvent is injected under selected conditions into an aqueous medium, with continual solvent removal. During the lipid injection and solvent-removal steps, the liposomes formed in the aqueous medium are extruded through a membrane, to reduce liposome sizes to less than about 0.6 microns. The lipid injection, solvent removal, and extrusion steps are continued until a lipid concentration of at least about 150 μm/ml is reached.
173 Citations
14 Claims
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1. A method of preparing a suspension of liposomes having a lipid concentration of greater than about 300 μ
- m/ml, and liposomes sizes no greater than about 0.4 microns, said method comprising
dissolving liposomes-forming lipids in a chlorofluorocarbon solvent, to form a lipid-in-solvent solution, injecting the lipid solution, in liquid form, into an aqueous medium, under pressure and temperature conditions at which lipid frothing is largely prevented, and at an injection rate that produces predominantly oligolamellar liposomes, during said injecting, removing injected chlorofluorocarbon solvent from the aqueous medium at substantially the same rate that it is introduced into the medium, also during said injecting, extruding liposomes formed in the aqueous medium to reduce the sizes of the largest liposomes to less than about 0.4 microns, and continuing said injecting, removing and extruding until the lipid concentration in the aqueous medium is at least about 300 μ
m/ml. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
- m/ml, and liposomes sizes no greater than about 0.4 microns, said method comprising
Specification