Periodic Reporting for period 1 - MONAGEL (anti-pseudoMOnas aeruginosa biofilm NAno-in-hydroGEL)
Berichtszeitraum: 2022-01-01 bis 2023-12-31
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.
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.
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.
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.