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 lipo somes 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 in travenously, liposome mixtures prevented death of laboratory mice infected with lethal doses of Staphylococcus aureus or Strepto-coccus pneumoniae.

1 - 18 . (canceled) 
     
     
         19 . Empty liposomes comprising
 30% (w/w) or more cholesterol and sphingomyelin, or
 mixtures of
 empty liposomes comprising 30% (w/w) or more 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.   
     
     
         20 . Empty liposomes comprising
 30% (w/w) or more cholesterol and sphingomyelin, or
 mixtures of
 empty liposomes comprising 30% (w/w) or more cholesterol and sphingomyelin, or 
 phosphatidylcholine and sphingomyelin, 
 
 with other empty liposomes comprising lipids or phospholipids selected from the group consisting of cholesterol, sphingomyelins, ceramides, phosphatidylcholines, 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 19 .   
     
     
         21 . 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  claim 19 . 
     
     
         22 . 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 to  claim 19 . 
     
     
         23 . Liposome mixture of empty liposomes comprising or consisting of cholesterol and sphingomyelin with other empty liposomes comprising or consisting of phosphatidylcholine and sphingomyelin, and with empty liposomes consisting of sphingomyelin, for use in the treatment and prevention of bacterial infections according to  claim 19 . 
     
     
         24 . Liposome mixture of empty liposomes comprising or consisting of cholesterol and sphingomyelin with other empty liposomes comprising or consisting of phosphatidylcholine 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  claim 19 . 
     
     
         25 . Empty liposomes comprising cholesterol and sphingomyelin, or 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  claim 19 . 
     
     
         26 . Empty liposomes comprising cholesterol and sphingomyelin, or 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  claim 19 . 
     
     
         27 . The empty liposomes or the mixture of empty liposomes for use according to  claim 19 , wherein said use is the treatment of bacterial infections of a patient in need thereof, and wherein a therapeutically effective amount of said empty liposomes or said mixtures of empty liposomes is used. 
     
     
         28 . The empty liposomes or the mixtures of empty liposomes for use according to  claim 27 , wherein said therapeutically effective amount of said empty liposomes or said mixtures of empty liposomes is used before, after, together or in parallel with a standard antibiotic medication against the bacterial infection. 
     
     
         29 . The empty liposomes or the mixtures of empty liposomes for use according to  claim 19 , wherein said use is the prevention of a bacterial infection of a subject exposed to the risk of infection, wherein a preventive amount of said empty liposomes or said mixtures of empty liposomes is used. 
     
     
         30 . Lipid bilayers or lipid monolayers comprising 30% (w/w) or more cholesterol and sphingomyelin, and optionally phosphatidylcholine, covering non-lipid surfaces, for use in the treatment and prevention of bacterial infections. 
     
     
         31 . A mixture of empty liposomes comprising 30% (w/w) or more cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with other empty liposomes of defined lipid composition. 
     
     
         32 . A mixture according to  claim 31  of empty liposomes comprising cholesterol and sphingomyelin, or phosphatidylcholine and sphingomyelin, with empty liposomes consisting of sphingomyelin. 
     
     
         33 . A mixture according to  claim 31  of empty liposomes comprising cholesterol and sphingomyelin with other empty liposomes comprising phosphatidylcholine and sphingomyelin, and with empty liposomes consisting of sphingomyelin. 
     
     
         34 . A mixture according to  claim 31  of empty liposomes comprising cholesterol and sphingomyelin with other empty liposomes comprising phosphatidylcholine and sphingomyelin, with empty liposomes consisting of sphingomyelin, and with empty liposomes comprising cholesterol and phosphatidylcholine. 
     
     
         35 . A mixture according to  claim 19  of empty liposomes wherein some or all liposomes are modified with polyethylene glycol. 
     
     
         36 . A pharmaceutical composition comprising
 (i) empty liposomes comprising 30% (w/w) or more cholesterol and sphingomyelin, or of
 a mixture of 
 empty liposomes comprising 30% (w/w) or more cholesterol and sphingomyelin, or
 phosphatidylcholine and sphingomyelin, 
 
 with other empty liposomes of defined lipid composition; and 
   (ii) a further pharmaceutically active compound, wherein preferably said further pharmaceutically active compound is selected from an antibiotic, an anti-cancer agent, an anti-inflammatory drug, a vasopressor, a vasoconstrictor, a pain killer and an anti-toxin.