Abstract: A composition and method for treating a wound or surgical incision, by sustained-released delivery of epidermal growth factor (EGF). The composition includes a high-viscosity aqueous dispersion of negatively charged liposomes with liposome-entrapped EGF. The EGF/liposome composition is formed, in one embodiment of the invention, by suspending a lipid mixture typically containing equimolar amounts of neutral and negatively charged phopholipids and cholesterol in a low-conductivity aqueous medium containing EGF and a zwitterionic compound whose isoelectric point is between pH 5.5 and 8.5 to form a gel-like composition. One embodiment of the invention contains EGF entrapped by surface adsorption to the liposomes, for slow release from the composition.

Abstract: A suspension of heterogeneous size liposomes is passed through a polymer filter having a web-like construction providing a network of interconnected, tortuous-path capillary pores, and a membrane thickness of at least about 100 microns. The processed liposomes have a selected average size less than about 0.4 microns, and a narrow size distribution.

Abstract: An doxorubicin/lyposome composition which can be reconstituted from a lyophilized form to an injectable liposome suspension having selected liposome sizes in the size range between 0.1 and 0.5 microns, and between about 85-95% liposome-entrapped doxorubicin. The composition is prepared by reconstituting a lyophilized doxorubicin/liposome composition to a liposome concentrate, then diluting the concentrate for perenteral.

Abstract: This invention relates to a novel, non-conventional liposome formulation for the sustained release and delivery of steroids. The formulation provides prolonged release of the drug, improved therapeutic ratio, lower toxicity, reduced systemic side effects and is stable for several months.

Abstract: A system and method for administering a drug, at a selected dose, via the respiratory tract. Spray-dried liposome particles containing the selected dose of the entrapped drug are released into the air in aerosolized form, either by entrainment in an air or propellant stream, or by release from a pressurized can containing a suspension of the liposomes in a fluorchlorocarbon solvent.

Abstract: A method for enhancing the therapeutic effectiveness of adriamycin, in the treatment of cancer, is disclosed. Liposomes containing coentrapped adriamycin and a secondary compound effective to reduce the toxicity of adriamycin or enhance the induction by adriamycin of the tumoricidal activity of host lymphoid cells, such as lipopolysaccharide, are administered parenterally in a therapeutically effective dose. In another aspect, macrophages stimulated in vivo with liposomes containing entrapped liposomes are exposed to an immunostimulator, for enhanced tumoricidal activity. Also disclosed are liposome compositions containing coentrapped adriamycin and an immunostimulator.

Abstract: A liposome composition designed for enhanced binding to mucosal tissue, The liposomes contain about 10-40 mole percent of an amine-derivatized lipid component in which a charged amine group is spaced from a lipid polar head region by a carbon-containing spacer arm at least 3 atoms in length. The liposomes preferably have a close packed lipid structure produced by inclusion of between 20-50 mole percent of cholesterol or an amine-derivatized cholesterol, and/or phospholipids with predominantly saturated acyl chain moieties. For ophthalmic use, the liposomes may be suspended in an aqueous medium containing a high-viscosity polymer, to enhance further the retention of liposomes on a corneal surface.

Abstract: A composition of liposomes which contain an entrapped pharmaceutical agent and are characterized by: (a) liposome sizes predominantly between about 0.08 and 0.5 microns: (b) at least about 50 mole percent of a membrane-rigidifying component, such as sphingomyelin or neutral phospholipids with predominantly saturated acyl chains: and (c) between about 5-15 mole percent ganglioside G.sub.M1. The liposomes show a blood/RES tissue distribution ratio, two hours after intravenous administration, which is substantially greater than the sum of the distribution ratios observed with similarly constructed liposome compositions containing the membrane-rigidifying agent alone and gangliosides alone. Also disclosed are methods for enhancing the blood/RES ratio of intravenously administered liposomes, and for assessing the effect of selected liposome components on in vivo uptake of liposomes by cells of the reticuloendothelial system (RES).

Abstract: An aqueous, noncrystalline minoxidil composition for topical use. The composition contains minoxidil complexed with an amphipathic compound having a pK less than about 5 and containing a single lipophilic chain moiety and a sulfate, sulfonate, phosphate and phosphonate polar moiety. The composition may be formulated in ointment form, in an aqueous vehicle, or dispersed in a fluorochlorocarbon solvent, for spray delivery from a self-propelled spray device.

Abstract: An amphotericin B composition containing particles of amphotericin B and cholesterol sulfate, in a molar ratio of between about 1:1 to 1:4. The particles, when stored in lyophilized form and reconstituted in an aqueous suspension, have particle sizes predominantly between about 100-400 nm. The composition formed at a molar ratio of about 1:1 amphotericin B:cholesterol sulfate ahs stable particle sizes in an aqueous suspension over a several-day storage period. The composition is significantly less toxic and more effective in treating fungal infection than prior amphotericin B formulations.

Abstract: A liposome composition useful in the treatment of dry eye. The composition includes an aqueous suspension of liposomes whose lipid composition preferably includes about 70-85 mole percent of hydrogenated phosphatidylcholine, and 15-30 mole percent of benzyldimethylstearylammonium chloride. The suspension is stable on storage at room temperature for several months.

Abstract: A liposome composition with enhanced retention on ocular surfaces, for use in ophthalmic drug delivery and dry eye treatment. The liposomes contain about 10-40 mole percent of an amine-derivatized lipid component in which a charged amine group is spaced from a lipid polar head region by a carbon-containing spacer arm at least 3 atoms in length. The liposomes preferably have a close packed lipid structure produced by inclusion of between 20-50 mole percent of cholesterol or an amine-derivatized cholesterol, and/or phospholipids with predominantly saturated acyl chain moieties. The liposomes may be suspended in an aqueous medium containing a high-viscosity polymer, formulated in paste form, or embedded in a polymer matrix, to enhance further the retention of liposomes on a corneal surface.

Abstract: A method of preparing a concentrated liposome suspension having a lipid concentration of greater than about 250 .mu.m/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 .mu.m/ml is reached.

Abstract: A dehydrated liposome/amphotericin B composition which, upon addition of an aqueous medium, forms a suspension of liposomes (a) having a predetermined size distribution in size range less than about 1 micron, and (b) containing at least about 1 mole percent amphotericin B. The composition is prepared by forming a suspension of heterogeneous size amphotericin B liposomes in an aqueous solution containing at least about 0.5% of a membrane-stabilizing agent. The suspension is sized--for example, by extrusion through a small-pore polycarbonate membrane--to produce liposomes having the selected size distribution, and dehydrated.

Abstract: A lipid coupling reagent for use in coupling amine-containing molecules, such as proteins, to liposomes. The reagent includes phosphatidylethanolamine coupled to a 3-20 atom carbon-containing spacer arm terminating at a carboxyl or thiocarboxyl group. Also disclosed are liposomes prepared to include between about 1 and 20 mole percent of the coupling reagent, and liposomes containing surface arrays of proteins attached to the liposomes through the coupling reagent.

Abstract: A method of preparing a suspension of liposomes containing a water-soluble compound predominantly in liposome-encapsulated form. A solution of vesicle-forming lipids in a chlorofluorocarbon solvent is infused under selected conditions into an aqueous medium, with continual solvent removal. The lipid infusion and solvent removal steps are continued until a lipid concentration of at least about 150 .mu.m/ml is reached, at which point more than about half of the compound contained in the resultant liposome suspension is in encapsulated form.

Abstract: A suspension of liposomes whose sizes are predominantly greater than about 1 micron is passed through an asymmetric ceramic filter whose inner-surface pore size is about 1 micron. The processed liposomes have a selected average size of about 0.4 microns or less, depending on the number of filter cycles, and a narrow distribution.