Liposomes for inhibiting biofilm formation

Abstract

The present invention relates to a composition comprising, preferably consisting of, (i) a single empty liposome, wherein said single empty liposome is selected from (a) an empty liposome comprising cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight), wherein preferably said empty liposome comprising, further preferably consisting of, cholesterol and sphingomyelin; or (b) an empty liposome consisting of sphingomyelin; or (ii) a mixture of empty liposomes; wherein said mixture of empty liposomes comprises, preferably consists of, at least one empty liposome selected from (a) an empty liposome comprising cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight), wherein preferably said empty liposome comprising, further preferably consisting of, cholesterol and sphingomyelin; (b) an empty liposome consisting of sphingomyelin; and (c) an empty liposome comprising, preferably consisting of, phosphatidylcholine and sphingomyelin; and at least one empty liposome independently of each other selected from an empty liposome comprising, preferably consisting of, lipids or phospholipids selected from cholesterol, sphingomyelins, ceramides, phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, diacylglycerols, and phosphatidic acids containing one or two or more saturated or unsaturated fatty acids longer than 4 carbon atoms and up to 28 carbon atoms; for use in a method for preventing or reducing biofilm formation or for eradicating or reducing existing biofilm.

1 . A composition comprising, preferably consisting of,
 (i) a single empty liposome, wherein said single empty liposome is selected from
 (a) an empty liposome comprising cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight), wherein preferably said empty liposome comprising, further preferably consisting of, cholesterol and sphingomyelin; or 
 (b) an empty liposome consisting of sphingomyelin; 
   
       or
 (ii) a mixture of empty liposomes, wherein said mixture of empty liposomes comprises, preferably consists of, at least one empty liposome selected from
 (a) an empty liposome comprising cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight), wherein preferably said empty liposome comprising, further preferably consisting of, cholesterol and sphingomyelin; 
 (b) an empty liposome consisting of sphingomyelin; and 
 (c) an empty liposome comprising, preferably consisting of, phosphatidylcholine and sphingomyelin; 
 
 and at least one empty liposome independently of each other selected from an empty liposome comprising, preferably consisting of, lipids or phospholipids selected from cholesterol, sphingomyelins, ceramides, phosphatidylcholines, phosphatidylethanol-amines, phosphatidylserines, diacylglycerols, and phosphatidic acids containing one or two or more saturated or unsaturated fatty acids longer than 4 carbon atoms and up to 28 carbon atoms; 
 
       for use in a method for preventing or reducing biofilm formation or for eradicating or reducing existing biofilm. 
     
     
         2 . The composition for use of  claim 1 , wherein said (i) single empty liposome is selected from (a) an empty liposome consisting of sphingomyelin and cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight); or (b) an empty liposome consisting of sphingomyelin; and wherein said mixture of empty liposomes comprises (a) a first empty liposome consisting of sphingomyelin and cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight); and (b) a second empty liposome consisting of sphingomyelin. 
     
     
         3 . The composition for use of  claim 1 , wherein said composition comprises, preferably consists of, a single empty liposome, wherein said single empty liposome is (a) an empty liposome consisting of sphingomyelin and cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight), or (b) an empty liposome consisting of sphingomyelin. 
     
     
         4 . The composition for use of  claim 1 , wherein said composition comprises, preferably consists of, a mixture of empty liposomes, wherein said mixture of empty liposomes comprises, preferably consists of, (a) a first empty liposome consisting of sphingomyelin and cholesterol, wherein the amount of cholesterol is at least 30% (weight per weight); and (b) a second empty liposome consisting of sphingomyelin. 
     
     
         5 . The composition for use of any one of the  claims 1  to  4 , wherein the amount of cholesterol of said empty liposome (a) is 30%-70% (weight per weight), and wherein preferably the amount of cholesterol of said empty liposome (a) is 35%-60% (weight per weight). 
     
     
         6 . The composition for use of any one of the  claims 1  to  5 , wherein the amount of cholesterol of said empty liposome (a) is 45%-55% (weight per weight), and wherein preferably the amount of cholesterol of said empty liposome (a) is about 50% (weight per weight). 
     
     
         7 . The composition for use of any one of the  claims 2 ,  4  to  6 , wherein said mixture of empty liposomes comprises at least 20% (weight per weight) of said first and said second empty liposome, and wherein preferably said mixture of empty liposomes comprises at least 30% (weight per weight) of said first and said second empty liposome. 
     
     
         8 . The composition for use of any one of the  claims 2 ,  4  to  7 , wherein said mixture of empty liposomes comprises at least 40% (weight per weight) of said first and said second empty liposome. 
     
     
         9 . The composition for use of any one of the  claims 1  to  8 , wherein said use is in a method for preventing or reducing biofilm formation on a surface or for use in a method for eradicating or reducing an existing biofilm on a surface. 
     
     
         10 . The composition for use of any one of the  claims 1  to  9 , wherein said use is for prophylaxis or treatment of a condition or disease, and wherein preferably said condition or disease is caused by bacteria present in said biofilm. 
     
     
         11 . The composition for use of  claim 10 , wherein said condition or disease is selected from an infection, and wherein preferably said infection is an airway infection, sexually-transmitted disease, meningitis, urinary infection, gastrointestinal disease, native valve endocarditis, colitis, vaginitis, urethritis, conjunctivitis, otitis, preferably otitis media, cystic fibrosis, ventilator-associated pneumonia, bacteremia, or wound infection. 
     
     
         12 . The composition for use of  claim 10  or  claim 11 , wherein said condition or disease, preferably said infection, is caused by at least one ESKAPE pathogen. 
     
     
         13 . The composition for use of any one of the  claims 10  to  11 , wherein said condition or disease is caused by Gram-negative bacteria or Gram-positive bacteria selected from  S. pneumoniae, Bacillus  spp,  Listeria monocytogenes, Staphylococcus  spp, lactic acid bacteria, preferably  Lactobacillus plantarum  and  Lactococcus lactis, Streptococcus sobrinus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa , Entersobacteriaceae,  Salmonella  species, preferably  Salmonella enterica, Salmonella enteritidis  or  Salmonella typhi, Actinobacillus pleuropneumoniae, Proteus mirabilis, Shigella species, Moraxella , preferably  Moraxella catarrhalis, Helicobacter , preferably  Helicobacter pylori, Stenotrophomonas, Bdellovibrio , acetic acid bacteria,  Legionella , preferably  Legionella pneumophila , cyanobacteria, spirochaetes, green sulfur, and green non-sulfur bacteria,  Neisseria , preferably  Neisseria gonorrhoeae  or  Neisseria meningitides, Haemophilus influenza, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens, Enterobacter cloacae  and  Enterobacter  spp. 
     
     
         14 . The composition for use of any one of the  claims 1  to  13 , wherein said use is in combination with an antimicrobial agent, wherein preferably said antimicrobial agent is an antibiotic, an antifungal agent, an anti-toxin agent, an anti-virulence agent, an antiseptic, or a combination thereof, and wherein further preferably said antimicrobial agent is an antibiotic. 
     
     
         15 . The composition for use of any one of the  claims 1  to  14 , wherein said method is an ex-vivo method, wherein preferably said method comprises contacting a surface, preferably a surface of a medical device, with a composition of any one of  claims 1  to  14 .