The Liposome Company, Inc.

Anthony G Durning

Andrew S Janoff

Pieter Rutter Cullis

Thomas D Madden

Robert P Lenk

Joel B Portnoff

John J Kearns

Robert J Klimchak

Joel Portnoff

Lawrence T Boni

Michelle L Tomsho

Robyne J Kelemen

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.

Methods of preparing low-toxicity drug-lipid complexes

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

The invention provides a method of separating liposomes or lipid complexes from a fluidic medium. The method involves passage of a fluidic medium containing liposomes or lipid complexes through a composite filter which retains the liposomes or lipid complexes while allowing the fluidic medium to pass through. The filter is composed of a ceramic membrane and a ceramic substrate that is thicker than the ceramic membrane. Moreover, the average pore size of the ceramic membrane, from about 0.1 to about 0.2 microns, is less than the average pore size of the substrate.

Method of separating materials from liposomes or lipid complexes

Low toxicity drug-lipid systems

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Yardley, PA, United States of America

Anthony G Durning