Liposomes with enhanced circulation time
AssigneeLiposome Technology, Inc.
InventorsMartin C. Woodle, Francis J. Martin, Annie Yau-Young, Carl T. Redemann
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Abstract
A liposome composition which contains between 1-20 mole percent of an amphipathic lipid derivatized with a polyalkylether, as exemplified by phosphatidylethanolamine derivatized with polyethyleneglycol. The derivatized lipid enchances the circulation time of the liposomes severalfold, and this enhancement is achieved with either fluid or membrane-rigidifying liposome components. Also disclosed are methods for delivering a drug for slow release from the bloodstream, and for targeting a selected tissue or cells with liposomes, via the bloodstream.
Claims33
A liposome composition for use in delivering a compound via the bloodstream comprising
- liposomes composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic, vesicle-forming lipid derivatized with a polyethyleneglycol, and containing the compound in liposome-entrapped form, and
- characterized by a blood level, 24 hours after intravenous injection, which is severalfold times that of the liposomes in the absence of the derivatized lipid.
A method of producing a severalfold increase in the blood-circulation time of intravenously administered liposomes formed of vesicle-forming lipids and containing an entrapped compound, as measured by the percent liposome marker retained in the blood 24 hours after intravenous injection, substantially independent of the degree of saturation of said vesicle-forming lipids, comprising
- forming the liposomes to include between about 1-20 mole percent an amphipathic, vesicle-forming lipid derivatized with a polyethyleneglycol.
A method of enhancing the uptake, by the reticuloendothelial system, of cells carrying surface-specific ligand-binding molecules which are characteristic of a disease state, comprising
- preparing a suspension of liposomes containing between 1-20 mole percent of an vesicle-forming lipid derivatized with a polyethyleneglycol, and a surface-bound ligand effective to bind specifically and with high affinity to said ligand-binding molecule, and
- administering said suspension intravenously.
A method of administering a compound intravenously, to achieve a level of compound in the bloodstream, 24 hours after drug administration, which is at least about 5 percent of the total amount of compound administered, comprising
- preparing a suspension of liposomes composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic, vesicle-forming lipid derivatized with a polyethyleneglycol, and the compound, in liposome-entrapped form, and
- intravenously administering an amount of the suspension containing a pharmacologically acceptable amount of the drug.
A method of delivering a drug selectively to a target tissue containing surface-bound tissue-specific ligand-bind molecules, comprising
- preparing a suspension of liposomes containing between 1-20 mole percent of an vesicle-forming lipid derivatized with a polyethyleneglycol, a surface-bound ligand effective to bind specifically and with high affinity to said ligand-binding molecule, and the drug, in liposome-entrapped form, and
- intravenously administering an amount of the suspension containing a pharmacologically acceptable amount of the drug.
Dependencies are inferred from the claim text.