Emulsion formulations for hydrophilic active agents
AssigneeUniversity of Pittsburgh
InventorsLeaf Huang, Toshifumi Hara
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Abstract
This invention includes emulsion formulations comprising an aqueous carrier and the following components: triglyceride, cholesterol, phospholipid, at least one charged lipid, at least one hydrophilic biologically active molecule and, optionally, cholesteryl ester, and/or apoprotein; methods of preparing these emulsions; and the use of these emulsions for the delivery of hydrophilic biologically active molecules to cells.
Claims22
An oil-in-water emulsion formulation comprising triglycerides, cholesterol, a cholesteryl ester, a first and a second lipid, a nucleic acid and an aqueous carrier, wherein the first lipid is a cationic lipid that forms a hydrophobic complex with the nucleic acid that is encapsulated within an apolar core comprising said triglycerides, and wherein the second lipid is a phospholipid, and wherein the weight ratio of nucleic acid to the sum of triglyceride, cholesterol, cholesteryl ester, and second lipid is about 1:50 to about 1:400.
An oil-in-water emulsion formulation produced by
- (a) mixing a hydrophobic complex of a first lipid and a nucleic acid with triglyceride, cholesterol, a cholesteryl ester, and a second lipid in an organic solvent, wherein the first lipid is a cationic lipid, and wherein the second lipid is a phospholipid;
- (b) removing said solvent to leave a lipid film;
- and
- (c) resuspending said film in aqueous carrier to produce the emulsion formulation,
- wherein the weight ratio of nucleic acid to the sum of triglyceride, cholesterol, cholesteryl ester, and second lipid in step (a) is about 1:50 to about 1:400.
A method of producing an oil-in-water emulsion comprising:
- a first lipid, a nucleic acid, triglyceride, cholesterol, a cholesteryl ester, a second lipid and an aqueous carrier, wherein the first lipid is a cationic lipid and wherein the second lipid is a phospholipid, said method comprising:
- (a) mixing a hydrophobic complex of the first lipid and nucleic acid with triglyceride, cholesterol, cholesteryl ester, and the second lipid in an organic solvent;
- (b) removing the organic solvent to leave a lipid film;
- and
- (c) suspending said film in an aqueous buffer to produce the emulsion,
- wherein the weight ratio of nucleic acid to the sum of triglyceride, cholesterol, cholesteryl ester, and second lipid in step (a) is about 1:50 to about 1:400.
A method for producing an oil-in-water emulsion comprising a first lipid, a nucleic acid, triglyceride, cholesterol, a cholesteryl ester, a second lipid, an aqueous carrier and optionally apoprotein, wherein the first lipid is a cationic lipid and wherein the second lipid is a phospholipid, said method comprising:
- (a) extracting native lipoprotein with an organic solvent;
- (b) mixing the extracted lipoprotein components with a hydrophobic complex of the first lipid and nucleic acid in an organic solvent;
- (c) removing the organic solvent to produce a lipid or a lipid:protein film;
- and
- (d) adding aqueous carrier to the film to produce the emulsion.
A method of producing a lipid film having a first lipid, a nucleic acid, cholesterol, a cholesteryl ester, triglyceride and a second lipid, wherein the first lipid is a cationic lipid and wherein the second lipid is a phospholipid, said method comprising:
- (a) mixing a hydrophobic complex of the first lipid and a nucleic acid with triglyceride, the second lipid, cholesterol, and cholesteryl ester in an organic solvent;
- and
- (b) removing said solvent to leave the lipid film,
- wherein the weight ratio of nucleic acid to the sum of triglyceride, cholesterol, cholesteryl ester, and second lipid in step (a) is about 1:50 to about 1:400.
Dependencies are inferred from the claim text.