Descrizione del progetto
Idrogel innovativo come vettore per aiutare nella lotta contro i biofilm di Pseudomonas aeruginosa
Il batterio aerobico gram-negativo Pseudomonas aeruginosa (PA) è molto comune e presenta avanzati meccanismi di multifarmacoresistenza. Provoca malattie nelle piante, negli animali e negli esseri umani ed è correlato a infezioni mortali contratte in ospedale. Il PA può formare biofilm, ovvero comunità batteriche strutturate mille volte meno sensibili agli antibiotici. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto MONAGEL propone di combattere i biofilm di PA sviluppando un idrogel composto da nanoparticelle lipidiche reticolate con principi attivi idrofobici e idrofili incapsulati. L’applicabilità e l’efficacia dell’approccio saranno valutate in varie linee cellulari e dimostrate su un modello di co-cultura epitelio/biofilm come prova di concetto per un ulteriore sviluppo.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
38124 Braunschweig
Germania