Tailored liposomes for the treatment of bacterial infections

Abstract

The invention relates to the use of empty liposomes of defined lipid composition or mixtures of empty liposomes of defined lipid composition and to the use of other lipid bilayers or monolayers of defined lipid composition for the treatment and prevention of bacterial infections. It has been found that such liposomes, in particular a two-and a four-component mixture of liposomes comprising cholesterol and sphingomyelin, liposomes consisting of sphingomyelin, liposomes comprising sphingomyelin and phosphatidylcholine, and liposomes comprising cholesterol and phosphatidylcholine efficiently sequestrate a variety of toxins secreted by bacteria, thus preventing binding of bacterial toxins to target cells and toxin-induced lysis of the target cells. Injected intravenously, liposome mixtures prevented death of laboratory mice infected with lethal doses of Staphylococcus aureus or Streptococcus pneumoniae.

1 . Empty liposomes comprising cholesterol and sphingomyelin, and mixtures of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition for use in the treatment and prevention of bacterial infections. 
     
     
         2 . Empty liposomes comprising cholesterol and sphingomyelin, and mixtures of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes comprising lipids or phospholipids selected from the group consisting of cholesterol, sphingomyelins, ceramides, phosphatidyl-cholines, phosphatidylethanolamines, phosphatidylserines, diacylglycerols, and phosphatidic acids containing one or two saturated or unsaturated fatty acids longer than 4 carbon atoms and up to 28 carbon atoms, for use in the treatment and prevention of bacterial infections according to  claim 1 . 
     
     
         3 . Empty liposomes comprising sphingomyelin and 30% (w/w) or more cholesterol, and mixtures of empty liposomes comprising sphingomyelin and 30% (w/w) or more cholesterol with other empty liposomes of defined lipid composition, for use in the treatment and prevention of bacterial infections according to  claim 1  or  2 . 
     
     
         4 . Liposome mixture of empty liposomes comprising or consisting of cholesterol and sphingomyelin, with other empty liposomes comprising or consisting of sphingomyelin, for use in the treatment and prevention of bacterial infections according to any one of  claims 1  to  3 . 
     
     
         5 . Liposome mixture of empty liposomes comprising or consisting of phosphatidylcholine and sphingomyelin, with other empty liposomes comprising or consisting of sphingomyelin, for use in the treatment and prevention of bacterial infections according  claim 1  or  2 . 
     
     
         6 . Liposome mixture of empty liposomes comprising or consisting of cholesterol and sphingomyelin with other empty liposomes comprising or consisting of phosphatidyl-choline and sphingomyelin, and with empty liposomes consisting of sphingomyelin, for use in the treatment and prevention of bacterial infections according to any one of  claims 1  to  5 . 
     
     
         7 . Liposome mixture of empty liposomes comprising or consisting of cholesterol and sphingomyelin with other empty liposomes comprising or consisting of phosphatidyl-choline and sphingomyelin, with empty liposomes consisting of sphingomyelin, and with empty liposomes comprising or consisting of cholesterol and phosphatidylcholine, for use in the treatment and prevention of bacterial infections according to any one of  claims 1  to  6 . 
     
     
         8 . Empty liposomes comprising cholesterol and sphingomyelin, and mixtures of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition, wherein some or all liposomes are modified with polyethylene glycol, for use in the treatment and prevention of bacterial infections according to any one of  claims 1  to  7 . 
     
     
         9 . Empty liposomes comprising cholesterol and sphingomyelin, and mixtures of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition, for use in the treatment and prevention of bacteremia, bacterially infected skin lesions, meningitis and respiratory tract infections, according to any one of  claims 1  to  8 . 
     
     
         10 . Lipid bilayers or lipid monolayers comprising cholesterol and sphingomyelin, and optionally phosphatidylcholine, covering non-lipid surfaces, for use in the treatment and prevention of bacterial infections. 
     
     
         11 . A mixture of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition. 
     
     
         12 . A mixture according to  claim 11  of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with empty liposomes consisting of sphingomyelin. 
     
     
         13 . A mixture according to  claim 11  or  12  of empty liposomes comprising cholesterol and sphingomyelin with other empty liposomes comprising phosphatidylcholine and sphingomyelin, and with empty liposomes consisting of sphingomyelin. 
     
     
         14 . A mixture according to any one of  claims 11  to  13  of empty liposomes comprising cholesterol and sphingomyelin with other empty liposomes comprising phosphatidyl-choline and sphingomyelin, with empty liposomes consisting of sphingomyelin, and with empty liposomes comprising cholesterol and phosphatidylcholine. 
     
     
         15 . A mixture according to any one of  claims 11  to  14  of empty liposomes wherein some or all liposomes are modified with polyethylene glycol. 
     
     
         16 . A method of treating bacterial infections comprising administering to a patient in need thereof a therapeutically effective amount of empty liposomes comprising cholesterol and sphingomyelin, or of a mixture of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition. 
     
     
         17 . A method of preventing a bacterial infection comprising administering to a subject exposed to the risk of infection a preventive amount of empty liposomes comprising cholesterol and sphingomyelin, or of a mixture of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition effective for protection. 
     
     
         18 . A method of treating bacterial infections comprising administering to a patient in need thereof a therapeutically effective amount of empty liposomes comprising cholesterol and sphingomyelin, or of a mixture of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition before, after, together or in parallel with a standard antibiotic medication against the bacterial infection.