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Liposomes for inhibiting biofilm formation

Inactive Publication Date: 2020-07-23
COMBIOXIN SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method to prevent or reduce the formation of biofilm and to eradicate or reduce existing biofilm using empty liposomes of defined lipid composition and mixtures thereof. This approach can be applied to prevent and treat conditions and diseases such as acute and chronic bacterial infections or cystic fibrosis. Additionally, disrupting or weakening a biofilm or avoiding or decreasing biofilm formation via the empty liposomes of the invention can lead to an improved efficacy of subsequently applied anti-microbial agents, which can eliminate planktonic organisms and prevent spreading of infection to other parts of the body. The inventive compositions are believed to be non-toxic, which makes them advantageous in terms of safety and efficacy.

Problems solved by technology

Biofilms are also an issue in food industries due to the ability of biofilms to form on food equipment surfaces in food plants and during industrial processes.
Biofilm-associated infections are chronic, persistent and difficult to cure.
Even in the case of biofilm formed on implants such as cardiac valves, detached biofilm cells can migrate along with the bloodstream and cause infection in other organs.
Furthermore, antibiotic treatments targeted to infections using only planktonic bacteria are most often ineffective against the biofilm phenotype.
Effective antibiotic doses for biofilm eradication are hardly reached by conventional antibiotic administrations due to the toxicities and the side effects of high doses of antibiotics and due to the limitation of renal and hepatic functions.
Similarly, fungal biofilm-associated infections are frequently refractory to conventional therapy because of resistance to antimicrobial agents, due in part due to the surface-induced upregulation of drug efflux pumps.
However, although antibiotic and anti-fungal agents directly target the organisms forming the biofilm, they hardly succeed in treating biofilm-associated conditions.
Current methods are in fact not always successful in eradicating the infection, and infections involving biofilm-residing bacteria or fungi often turn out to be untreatable and eventually develop into a chronic state.
Despite the fact that the ability to form biofilms is a universal attribute of bacteria and that many medically important fungi produce biofilms, the precise mechanisms underlying biofilm formation are still not well understood which cause biofilm-associated infections to be particularly difficult to treat and eradicate.
Treatment of biofilm-related conditions has proven a considerable unmet clinical need.

Method used

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  • Liposomes for inhibiting biofilm formation

Examples

Experimental program
Comparison scheme
Effect test

example 1

Inhibition of P. aeruginosa Multi-Drug Resistant Strain 6077 Biofilm

[0150]A preferred inventive mixture of empty liposomes proved to decrease biofilm formation by Pseudomonas aeruginosa strain 6077, as revealed by the Crystal violet method. Said preferred inventive mixture of empty liposomes consists of a 1:1 (weight per weight—w / w) mixture of said first empty liposomes and said second liposomes, wherein said first empty liposome is composed of a 1:1 weight ratio (1:1 w / w; 35:65 molar ratio) of sphingomyelin (SM) and cholesterol (CHOL), and said second empty liposomes is composed exclusively of SM.

Method

[0151]Briefly, Pseudomonas aeruginosa strain 6077 was grown in Trypticase Soy Broth (TSB) and diluted in LB broth containing 2% glucose to a concentration of 1×107 or of 1×106 colony forming units (CFU) per mL. One hundred microliters (100 μl) of the diluted inoculum was added to the wells of a 96-well flat-bottomed microtiter plate. Increasing concentrations of preferred inventive m...

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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.

Description

[0001]The present invention relates to empty liposomes or mixtures of empty liposomes of defined lipid composition for preventing or reducing biofilm formation or for eradicating or reducing existing biofilm. The present invention further relates to a treatment or prophylaxis of such biofilm formation by using the inventive empty liposomes or mixtures of empty liposomes, alone or in combination with standard antimicrobial treatment.RELATED ART[0002]References: Davies, Nat. Rev. Drug Discov. (2003) 2:114-122; Bjarnsholt et al., Nat. Rev. Drug Discov. (2013) 12:791-808; Wu et al. International Journal of Oral Science 7 (2015); Rasamiravaka et al. BioMed Research International Volume (2015); Bhattacharya et al. Expert Rev Anti Infect Ther. (2015) 13(12); Peneysan et al. Molecules (2015) 20; Rabin et al. Future Med. Chem. (2015) 7(4).[0003]Microorganisms can occur as planktonic organisms (in particular free-floating bacteria or fungi) or as biofilm (in particular biofilm bacteria or fun...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/045A61K31/685A61K31/688A61L2/18
CPCA61L2202/24A61K31/685A61K31/045A61K9/127A61K31/688A61L2/18A61K47/28A61K47/24A61P31/04Y02A50/30
Inventor AZEREDO DA SILVEIRA LAJAUNIAS, SAMAREHLAJAUNIAS, FRÉDÉRIC
Owner COMBIOXIN SA
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