Encapsulation of ionizable agents in liposomes

US5837279A · kind A · utility

Assignee

• The Lipsome Company, Inc. · US

Inventors

• Andrew S. Janoff · Yardley, US
• Pieter R. Cullis · Vancouver, CA
• Marcel Bally · Bruce Mines, CA
• Michael W. Fountain · Plainsboro, US
• Richard S. Ginsberg · Jamesburg, US
• Michael J. Hope · Vancouver, CA
• Thomas D. Madden · Vancouver, CA
• Hugh P. Schieren · Yardley, US
• Regina L. Jablonski · Trenton, US

Key dates

• Filing date: May 25, 1995
• Grant date: Nov 17, 1998
• Expiry date: May 25, 2015

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P35/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.