Researchers have developed a novel apoptotic body like liposomes carrying bioactive lipids (ABL). ABL were shown to induce phagolysosome maturation and to promote a ROS dependent bactericidal innate immune response against Pseudomonas aeruginosa, in CF macrophages and in bronchoalveolar lavage cells from patients with multidrug resistant (MDR) pulmonary infections. Moreover, Metformin, an antidiabetic drug, has been reported to ameliorate in vitro sodium and fluid transport and reduce inflammation in Cystic Fibrosis (CF) airway epithelial cells while simultaneously enhancing autophagy mediated antimicrobial activity. To identify the ABL formulations, in combination or not with metformin, able to induce the best in vitro antimicrobial activity, macrophages coming from healthy volunteers and from CF patients will be infected with a panel of MDR P. aeruginosa strains; then selected compounds will be tested in CF mice model with P.a. acute infection. The main aim of this project is the development of a novel immunotherapeutic approach based on bioactive liposomes in combination or not with Metformin.
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