The Liposome Company, Inc.

Inex Pharmaceuticals Corporation

University of British Columbia

Celator Pharmaceuticals, Inc.

Bc Cancer Agency

The Lipsome Company, Inc.

Cullis, Pieter R.

Bally, Marcel B.

Madden, Thomas D.

Mayer, Lawrence D.

Hope, Michael J.

Marcel B Bally

Pieter Rutter Cullis

Michael J Hope

Lawrence D Mayer

Andrew S Janoff

Richard S Ginsberg

Jeffery J Wheeler

Thomas D Madden

Marco A Ciufolini

Paul Tardi

Igor V Jigaltsev

Murray Webb

Dorothy L Reimer

Norbert Maurer

Yuan-Peng Zhang

Helen C Loughrey

Michael W Fountain

Troy Harasym

Hugh P Schieren

Regina L Jablonski

George N Mitilenes

Clifford Shew

Peter Scherrer

Murray S Webb

Paul G Tardi

Euan Ramsay

James Jackson Miller

Sharon Johnstone

Lewis S Choi

Sheela Abraham

Jo Ann Jedrusiak

Robert P Lenk

Lois E Bolcsak

Kim F Wong

Jeffrey Jerome Wheeler

Nancy L Boman

Erik Swartz

Ellen K Wasan

Quet Fah Ahkong

Charmaine W Chang

Lana W Barber

Howard J Lim

Norbert Mauer

Pieter R Gullis

Andrew Janoff

Huge P Schieren

Fountain Michael W

Robert P Link

Compositions which comprise delivery vehicles having stably associated therewith non-antagonistic combinations of two or more agents, such as antineoplastic agents, are useful in achieving non-antagonistic effects when combinations of drugs are administered.

Compositions for delivery of drug combinations

Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Modified drugs for use in liposomal nanoparticles

The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Liposomes with improved drug retention for treatment of cancer

Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

This invention relates to encapsulation of drugs and other agents into liposomes.

Liposome loading with metal ions

Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer

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Vancouver, Canada

Marcel B Bally