Projektbeschreibung
Innovatives Hydrogel als Träger bei der Bekämpfung von Pseudomonas aeruginosa in Biofilmen
Pseudomonas aeruginosa ist ein weit verbreitetes gramnegatives aerobes Bakterium mit fortgeschrittenen Widerstandsmechanismen gegen mehrere Medikamente. Es verursacht Krankheiten bei Pflanzen, Tieren und Menschen und wird mit tödlichen Krankenhausinfektionen in Verbindung gebracht. Pseudomonas aeruginosa kann Biofilme bilden, also strukturierte Bakteriengemeinschaften, die um ein Tausendfaches weniger empfindlich auf Antibiotika reagieren. Das im Rahmen der Marie-Skłodowska-Curie-Maßnahmen geförderte Projekt MONAGEL schlägt vor, Biofilme mit Pseudomonas aeruginosa durch die Entwicklung eines Hydrogels zu bekämpfen, das aus vernetzten Lipidnanopartikeln mit eingeschlossenen hydrophoben und hydrophilen Wirkstoffen besteht. Die Anwendbarkeit und Wirksamkeit des Ansatzes wird in verschiedenen Zelllinien bewertet und der Konzeptnachweis für die Entwicklung mit einem Epithel-/Biofilmmodell in Co-Kultur demonstriert.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- engineering and technologynanotechnologynano-materials
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
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Aufforderung zur Vorschlagseinreichung
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
38124 Braunschweig
Deutschland