anti-pseudoMOnas aeruginosa biofilm NAno-in-hydroGEL

Informations projet

MONAGEL

N° de convention de subvention: 101024631

DOI

10.3030/101024631

Projet clôturé le 14 Juillet 2022

Date de signature de la CE 18 Juillet 2021

Date de début 1 Janvier 2022

Date de fin 31 Decembre 2023

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 174 806,40

Contribution de l’UE

€ 174 806,40

Coordonné par

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Germany

Periodic Reporting for period 1 - MONAGEL (anti-pseudoMOnas aeruginosa biofilm NAno-in-hydroGEL)

Période du rapport: 2022-01-01 au 2023-12-31

Résumé du contexte et des objectifs généraux du projet

Pseudomonas aeruginosa (PA) is an ubiquitous and opportunistic gram-negative bacterium infecting particularly immunocompromised hosts. Moreover, PA has the capability to protect itself from current antibiotics by turning into a biofilm form.
A new paradigm in research is that to fight biofilm infections, perturbating the biofilm might be a more effective strategy than using only classical antibiotics.Quorum sensing inhibition is such innovative strategy. Quorum sensing is the communication between bacteria regulating the biofilm. As the predictions of the WHO foresee the antibioresistance as one of the greatest danger of the 21st century, there is a dire need to create new strategies to fight bacterial infections.
To this end the concept of the MONAGEL is to formulate an inhalable lipid nanoparticles based hydrogel to create a differential release kinetic between hydrophilic antibiotics and lipophilic quorum sensing inhibitors to fight PA biofilms.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Sodium alginate was used to formulate hydrogels by crosslinking neutral and positive lipid nanocapsules of 25, 50 and 100 nm by simple mixing. Surprisingly the charge of the nanocapsules had no impact on the rheology of the gel which makes think that the association mechanism relies on hydrogen bonds between PEG and alginate. The rheology of the gel is sufficient for an extrusion by a needle and has shown good printability using a 3D bioprinter. Release studies with fluorescein show that the hydrophilic molecules inside of the hydrogel are liberated with the degradation of the gel in water. CryoTEM studies show that the lipid nanocapsules released from the hydrogel in water are not destructured.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

This work shows that crosslinking lipid nanocapsules is possible using a simple polymer with neither organic solvent nor high energy method. The hydrogel formation enables the coloading of hydrophilic and hydrophobic molecules paving the way for differential release profiles and integrated therapeutic regimen within one pharmaceutical form.

monagel.png