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anti-pseudoMOnas aeruginosa biofilm NAno-in-hydroGEL

Project description

Innovative hydrogel as a carrier to aid in the fight against Pseudomonas aeruginosa biofilms

Pseudomonas aeruginosa (PA) is a common gram-negative aerobic bacterium with advanced multidrug resistance mechanisms. It causes disease in plants, animals and humans and is associated with deadly hospital-acquired infections. PA can form biofilms, which are structured bacterial communities a thousand times less sensitive to antibiotics. Funded by the Marie Skłodowska-Curie Actions programme, the MONAGEL project proposes to combat PA biofilms by developing a hydrogel made of cross-linked lipid nanoparticles with encapsulated hydrophobic and hydrophilic active ingredients. The applicability and efficacy of the approach will be assessed in various cell lines and demonstrated on a co-culture epithelium/biofilm model as a proof of concept for further development.

Objective

Pseudomonas aeruginosa (PA) is ubiquitous gram-negative bacteria. PA is a serious threat and is considered as a critical priority for treatment development by various institutions such as the World Health Organization. PA can cause infections on various location such as eyes, lung, skin (wounds). Immunocompromised patients are especially at risk, as PA is also able to colonize domestic and hospital fixtures. To add insult to injury, the infection is hard to treat and the number of antibiotic resistant PA is on the rise. The major challenge opposed by PA is its biofilm. Biofilms are a structured bacterial community embedded in a matrix composed of exopolysaccharides, proteins, extracellular DNA, and lipids. PA present in the biofilm are a thousand times less sensitive to antibiotics than their planktonic form. The MONAGEL project propose to fight the PA in the biofilm by developing a hydrogel made of cross-linked lipid nanoparticles. The lipophilic core of the lipid nanoparticles will be used to encapsulate hydrophobic active ingredients, the aqueous cavities of the gel will be used to encapsulate hydrophilic ones. The hydrophobic and hydrophilic compartment will enable work with a broad variety of molecules such as fluorescent probes (which will permit a thorough characterisation of the gel) or active ingredients such as antibiotics and pathoblockers. The latter molecule will be efficient to design the gel towards fighting PA biofilm either by inhibiting quorum sensing (bacterial communication) or lectin interaction (key role in biofilm formation). Well thought work and contingency plans have been put in place to ensure the success of MONAGEL development. The innocuity of the system will be assessed on various cell lines, and the antibiofilm efficacy will be tested on in vitro models. In the end, the MONAGEL efficacy will be demonstrated on a co-culture model (epithelium + biofilm) as a proof-of-concept to serve as a selling point for further development.

Coordinator

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Net EU contribution
€ 174 806,40
Address
INHOFFENSTRASSE 7
38124 Braunschweig
Germany

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Region
Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost
€ 174 806,40