The Liposome Company, Inc.

Luna Innovations Inc.

Robert P Lenk

Andrew S Janoff

Michael W Fountain

Mircea C Popescu

Marc J Ostro

Robert J Klimchak

Michelle L Tomsho

Alan L Weiner

Stephen R Wilson

Richard S Ginsberg

Robert L Suddith

Steven J Weiss

Zhiguo Zhou

Darren K Macfarland

Carl R Alving

Kenneth L Walker

Paul A Tremblay

Joel B Portnoff

Anthony G Durning

Sol M Gruner

Joel Portnoff

Pieter Rutter Cullis

Marcel B Bally

Lawrence D Mayer

Thomas D Madden

Lawrence T Boni

Lois E Bolcsak

Sharma R Minchey

Christine E Swenson

John J Kearns

Sharon S Carpenter-Green

Micrea C Popescu

Christopher L Kepley

Jing Zhang

Rajesh Shukla

Sterling C Johnson

Jo Ann Jedrusiak

Mathew Cherian

Frank Pilkiewicz

Christopher Kepley

Endohedral metallofullerene compounds, which in water has a relaxivity of about 30 mMSto about 300 mMSand forms a dispersion in water with entities having an average hydrodynamic radius of less than about 20 nm.

Metallofullerene contrast agents

Described herein are methods for treating inflammatory disorders. The methods comprise administering to a subject in need thereof a therapeutically effective amount of a synthetically modified fullerene.

Fullerene therapies for inflammation

Described herein are synthetically modified fullerene molecules, wherein the fullerene is preferably ellipsoid in shape with an equatorial band and two opposing poles, comprising an adduct at one or both poles, at least one adduct being a hydrophobic chemical moiety capable of anchoring the fullerene on or in a lipid membrane.

Amphiphilic or lipophilic polar functionalized fullerenes and their uses

Tangential flow filtration is used in the size separation of particles, such as liposomes and lipid particles. These particles may be passed through a tangential flow filtration device of any pore size desired. Tangential flow filter systems of various pore sizes may be used sequentially to obtain particles such as lipid particles or liposomes having a defined size range.

Method for size separation of particles

This invention provides a multilamellar liposome containing an arachidonic acid metabolite, two or more lipid-containing bilayers and two or more aqueous compartments containing a release-inhibiting buffer. Preferred arachidonic acid metabolites are the prostaglandins, particularly PGE.sub.1. The liposomal formulations can be used to treat animals, particularly humans, for diseases, disorders or conditions which can be ameliorated by prostaglandins, e.g., disorders characterized by cellular activation and adhesion, inflammation and/or toxemia.

Therapeutic use of multilamellar liposomal prostaglandin formulations

Methods and compositions are described for nonliposomal lipid complexes in association with toxic hydrophobic drugs such as the polyene antibiotic amphotericin B. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio. The lipid complexes contain a bioactive agent, and may be made by a number of procedures, at high drug:lipid ratios. These compositions of high drug:lipid complexes (HDLCs) may be administered to mammals such as humans for the treatment of infections, with substantially equivalent or greater efficacy and reduced drug toxicities as compared to the drugs in their free form. Also disclosed is a novel liposome-loading procedure, which may also be used in the formation of the HDLCs.

Low toxicity drug-lipid systems

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 liposome composition and methods for making same are disclosed, such compositions comprise an arachidonic acid metabolite such as a prostaglandin, preferably prostaglandin E.sub.1, a lipid, and a drying protectant such as a saccharide. The liposomes may be loaded with prostaglandin passively, or using a transmembrane concentration gradient, preferably using a transmembrane pH gradient. Using this transmembrane loading technique, trapping efficiencies of 50% to 100% are achieved, and the release rate of the prostaglandin from the liposomes is reduced. The liposome size is maintained after lyophilization and reconstitution.

Prostaglandin-lipid formulations

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

A method of treating, by intramammary infusion of liposomes, Brucella spp. infections in an animal by administration of a therapeutically effective amount of aminoglycoside in liposome form, also being a method of administering a therapeutic agent in liposome form to a proximal mammary lymph node or mammary tissue of an animal.

Therapeutic treatment by intramammary infusion

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Lambertville, NJ, United States of America

Robert P Lenk