The Liposome Company, Inc.

The Lipsome Company, Inc.

Janoff, Andrew S.

Schieren, Hugh P.

Ginsberg, Richard S.

Jablonski, Regina L.

Fountain, Michael W.

Hope, Michael J.

Cullis, Pieter R.

Madden, Thomas D.

Bally, Marcel B.

Michael W Fountain

Andrew S Janoff

Mircea C Popescu

Robert P Lenk

Richard S Ginsberg

Marc J Ostro

Steven J Weiss

Pieter Rutter Cullis

Marcel B Bally

Michael J Hope

Alan L Weiner

Thomas D Madden

Hugh P Schieren

Regina L Jablonski

Carl R Alving

Paul A Tremblay

Sol M Gruner

John J Kearns

Sharon S Carpenter-Green

Micrea C Popescu

Huge P Schieren

Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration. Concentration gradients capable of generating transmembrane potentials can be created across the liposome membranes either before or after dehydration, and the transmembrane potentials resulting from these gradients can be used to load charged materials, e.g., drugs, into the liposomes.

Methods of dehydrating, storing and rehydrating liposomes

Encapsulation of ionizable agents in liposomes

Method of dehydrating liposomes using protective sugars

This invention encompasses new and substantially improved methods and compositions for delivery of therapeutic agents to specifically chosen body sites. Conjugation of fibronectin to bioactive agents or to lipids or to liposomes which entrap the bioactive agents permits immobilization of the bioactive agent when administered at collagen-, heparin-, hyaluronic acid-, fibrin/fibrinogen-, or ganglioside-rich sites. Covalent conjugation is achieved by two methods: (1) the enzymatically catalyzed cross-linkage of fibronectin to an amine containing compound, and (2) by a modified NHS method which permits formation of peptide bonds between fibronectin and lipid compounds.

Localized delivery using fibronectin conjugates

A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same and X-ray diffraction methods for identifying the same. SPLVs are characterized by lipid bilayers enclosing aqueous compartments containing one or more entrapped solutes, the concentration of such solutes in each aqueous compartment being substantially equal to the emunization of solutes used to prepare the SPLVs. The bilayers of SPLVs are substantially non-compressed. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

Stable plurilamellar vesicles

Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.

Drug preparations of reduced toxicity

A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same and X-ray diffraction methods for identifying the same. SPLVs are characterized by lipid bilayers enclosing aqueous compartments containing one or more entrapped solutes, the concentration of such solutes in each aqueous compartment being substantially equal to the concentration of solutes used to prepare the SPLVs. The bilayers of SPLVs are substantially non-compressed. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

The invention encompasses mixtures of antimicrobial agents coencapsulated in liposomes which when administered in vivo exert an enhanced therapeutic effect. The therapeutic effectiveness of the coencapsulated antimocrobial agents is greater than that of the same combination administered either in solution or as a mixture of liposome populations each containing one of the antimicrobial agents.

Enhancement of pharmaceutical activity

Dehydrated liposomes

Lipid matrix carriers are described which provide for the sustained release of bioactive agents in vivo or in vitro. The properties of the lipid matrix carriers of the present invention include high entrapment efficiencies; release of entrapped compounds in their active form; biodegradability and avoidance of vascular occlusion in vivo; and avoidance of sequestration of the bioactive agent in the liver and spleen.

Lipid matrix carriers for use in drug delivery systems

A process for the preparation in a monophasic solvent system of a new type of lipid vesicles, called monophasic lipid vesicles (MPVs). MPVs can be made to encapsulate one or more bioactive agents. MPVs are stable during storage and can be used in vivo in the treatment of disease.

Lipid vesicles prepared in a monophase

A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

Stable plurilamellar vesicles, their preparation and use

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Griggstown, NJ, United States of America

Michael W Fountain