Stable plurilamellar vesicles, their preparation and use

Claim 3

The method according to claim 1, wherein the ratio of volume of solvent to volume of aqueous phase is from about 3:1 to about 100:1.

Claim 4

The method according to claim 1, wherein the temperature at which the method is performed is from about 4° C. to about 60° C.

Claim 5

The method according to claim 1, wherein the temperature at which the method is performed is less than the phase transition temperature of at least one of said lipids.

Claim 6

The method according to claim 1, wherein the solvent is fluorocarbon or diethylether, or mixtures thereof.

Claim 7

The method according to claim 5 wherein the solvent contains an anti-oxidant.

Claim 8

The method according to claim 6, wherein said anti-oxidant is butylated hydroxytoluene.

Claim 9

The method according to claim 1 wherein a material to be entrapped in the vesicles is added with the aqueous phase.

Claim 10

The method according to claim 8, wherein at least 20 percent of said material is entrapped in the vesicles.

Claim 11

The method according to claim 8, wherein said material is a protein.

Claim 12

Stable plurilamellar vesicles comprising lipid vesicles ranging from about lOO nm to about 10,000 nm in size, characterized by a few to over 100 lipid bilayers enclosing aqueous compartments containing at least one entrapped solute in which the lipid bilayers have an ordered molecular architecture creating a supramolecular structure which differs from that of other multilamellar vesicles so that when compared to other multilamellar vesicles composed of the identical lipid and aqueous ingredients, stable plurilamellar vesicles have the following properties: (a) a higher percent entrapment of solute; (b) a lower buoyant density; (c) a volume about one-third larger; (d) greater stability to auto-oxidation during storage in buffer; (e) greater stability in body fluids; (f) a larger percent leakage of entrapped solute when exposed to urea, guanidine, or ammonium acetate; (g) a smaller percent leakage of entrapped solute when exposed to hydrochloric acid or serum; and (h) distribution of entrapped contents throughout the cytosol of cells when administered to the cells in culture.

Claim 13

Stable plurilamellar vesicles comprising lipid vesicles ranging from about lOO nm to about 10,000 nm in size, characterized by a few to over 100 lipid bilayers enclosing aqueous compartments containing at least one entrapped solute in which the lipid bilayers have an ordered molecular architecture creating a supramolecular structure which differs from that of other multilamellar vesicles so that when compared to other multilamellar vesicles composed of the identical lipid and aqueous ingredients, stable plurilamellar vesicles have the following properties: (a) a higher percent entrapment of solute; (b) a lower buoyant density; (c) a volume about one-third larger; (d) greater stability to auto-oxidation during storage in buffer; (e) greater stability in body fluids; (f) a larger percent leakage of entrapped solute when exposed to urea, guanidine, or ammonium acetate; (g) a smaller percent leakage of entrapped solute when exposed to hydrochloric acid or serum; and (h) distribution of entrapped contents throughout the cytosol of cells when administered to the cells in culture.

Claim 14

Stable plurilamellar vesicles according to claim 11 substantially free of MLVs, SUVs, and REVs.

Claim 15

The stable plurilumellar vesicles of claim 11 in which the lipid bilayers comprise a phospholipid.

Claim 16

The stable plurilamellar vesicles of claim 13 in which the phospholipid is amphipathic.

Claim 17

Stable plurilamellar vesicles according to claim 11, wherein the major lipid component of the vesicles is a phosphatidylcholine.

Claim 18

Stable plurilamellar vesicles according to claim 11, wherein an anti-oxidant is a component of the vesicle.

Claim 19

Stable plurilamellar vesicles according to claim 16 wherein said anti-oxidant is butylated hydroxytoluene.

Claim 20

Stable plurilamellar vesicles according to claim 12, wherein a protein is entrapped within the vesicle.

Claim 21

Stable plurilamellar vesicles according to claim 12, wherein a compound selected from the group consisting of: antibacterial compounds, antifungal compounds, antiparasitic compounds, and antiviral compounds is entrapped within the vesicle.

Claim 22

Stable plurilamellar vesicles according to claim 11, wherein a compound selected from the group consisting of: tumoricidal compounds, toxins, cell receptor binding molecules, and immunoglobulins is entrapped within the vesicle.

Claim 23

Stable plurilamellar vesicles according to claim 11, wherein a compound selected from the group consisting of: anti-inflammatory compounds, anti-glaucoma compounds, mydriatic compounds, and local anesthetics is entrapped within the vesicle.

Claim 24

Stable plurilamellar vesicles according to claim 11, wherein a compound selected from the group consisting of: enzymes, hormones, neurotransmitters, immunomodulators, nucleotides, and cyclic adenosine monophosphate is entrapped within the vesicle.

Claim 25

Stable plurilamellar vesicles according to claim 11, wherein a compound selected from the group consisting of: dyes, fluorescent compounds, radioactive compounds, and radio-opaque compounds is entrapped within the vesicle.

Claim 26

A method for delivery of a compound to cells in vivo, comprising: administering to an organism stable plurilamellar vesicles of claim 11 containing said compound entrapped therein.

Claim 27

The method according to claim 24, wherein said stable plurilamellar vesicles are administered topically, intraperitoneally, intravenously, intramuscularly, subcutaneously or intraauricularly.

Claim 28

A method for treatment of infections in animals or plants, comprising: administering stable plurilamellar vesicles of claim 11 containing a compound effective for treating said infection.

Claim 29

The method according to claim 26, wherein said infection is intracellular.

Claim 30

The method according to claim 27 wherein said infection is caused by a parasite.

Claim 31

The method according to claim 28, wherein said infection is caused by Brucella spp.

Claim 32

The method according to claim 29, wherein said administration is intraperitoneal.

Claim 33

The method according to claim 26, wherein said infection is extracellular.

Claim 34

The method according to claim 31 wherein said infection is caused by bacteria.

Claim 35

The method according to claim 32, wherein said infection is caused by Staphylococcus aureus.

Claim 36

The method according to claim 33, wherein said administration is intraperitoneal.

Claim 37

The method according to claim 26, wherein said infection is an ocular infection.

Claim 38

The method according to claim 35, wherein said infection is caused by a Moraxella spp.

Claim 39

The method according to claim 36, wherein said administration is topical.

Claim 40

The method according to claim 26, wherein said infection is caused by a virus.

Claim 41

The method according to claim 38, wherein said infection is caused by lymphocytic choriomeningitis virus.

Claim 42

The method according to claim 39, wherein said administration is intraperitoneal.

Claim 43

A method for treatment of afflictions in animals or plants requiring sustained release of a compound effective for treating said affliction, comprising: administering stable plurilamellar vesicles of claim 11 containing said compound.

Claim 44

The method according to claim 41, wherein said affliction is an ocular affliction.

Claim 45

A method according to claim 42, wherein said affliction is glaucoma.

Claim 46

The method according to claim 43, wherein said administration is topical.