anti-pseudoMOnas aeruginosa biofilm NAno-in-hydroGEL

Descripción del proyecto

Un hidrogel innovador como portador para ayudar en la lucha contra las biopelículas de «Pseudomonas aeruginosa»

La «Pseudomonas aeruginosa» (PA) es una bacteria aeróbica gramnegativa común con mecanismos avanzados de multirresistencia. Causa enfermedades en las plantas, los animales y los seres humanos y está asociada a infecciones mortales nosocomiales. Las PA pueden formar biopelículas, que son comunidades bacterianas estructuradas mil veces menos sensibles a los antibióticos. El equipo del proyecto MONAGEL, financiado por las Acciones Marie Skłodowska-Curie, propone combatir las biopelículas de PA desarrollando un hidrogel compuesto por nanopartículas lipídicas reticuladas con principios activos hidrofóbicos e hidrófilos encapsulados. La aplicabilidad y eficacia del enfoque se evaluará en diferentes líneas celulares y se demostrará en un modelo de cocultivo de epitelio/biopelícula como prueba de concepto para su posterior desarrollo.

Objetivo

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.