Fused liposome and acid induced method for liposome fusion
First Claim
1. A method of fusing liposomes which comprises:
- (a) preparing a suspension of liposomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least 20 mol percent of palmitoylhomocysteine; and
(b) in the absence of externally added divalent cations, proteins or other macromolecules, acidifying the liposome suspension to reduce the pH of the liposomes to below pH 7, such that at least about 20% of said liposomes fuse to one another.
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Accused Products
Abstract
Liposomes containing phosphatidylethanolamine, palmitoyl homocysteine or oleic acid or palmitic acid, fuse rapidly when the pH of the medium is reduced below 7. Liposome fusion was measured by (a) mixing of the liposomal lipids as shown by resonance energy transfer, (b) gel filtration and (c) electron microscopy. The presence of phosphatidylethanolamine or acid addition esters thereof in the liposomes greatly enhances fusion; whereas the presence of phosphatidylcholine inhibits fusion. During fusion of liposomes containing phosphatidylethanolamine:palmitoyl homocysteine (8:2), almost all of the encapsulate calcein is released. Inclusion of cholesterol (40%) in the liposomes substantially decreases leakage without impairing fusion. Those pH sensitive liposomes are fused to deliver biologically active molecules such as DNA, into living cells.
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Citations
9 Claims
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1. A method of fusing liposomes which comprises:
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(a) preparing a suspension of liposomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least 20 mol percent of palmitoylhomocysteine; and (b) in the absence of externally added divalent cations, proteins or other macromolecules, acidifying the liposome suspension to reduce the pH of the liposomes to below pH 7, such that at least about 20% of said liposomes fuse to one another. - View Dependent Claims (2, 3)
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4. A method of inserting foreign material into a living cell which comprises:
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(a) encapsulating the foreign material in non-leaky, pH sensitive liposomes prepared from cholesterol, at least one lipid which has a tendency to form the inverted hexagonal phase and at least about 20 mol percent of palmitoyl homocysteine; and (b) in the absence of externally added divalent cations, proteins, or macromolecules, containing said living cell, at its physiologicla pH, with said encapsulated, non-leaky, pH sensitive liposomes, whereby insertion occurs. - View Dependent Claims (5, 6)
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- 7. Liposomes, fused to one another at a pH of less than about 6.5, at a fusion level of at least about 50%, said lipsomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least about 20 mol percent of palmitoyl homocysteine.
Specification