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Novel cationic glycoliposomes, composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol (Chol) and glycoamphiphiles featuring a galactosyl, mannosyl or glucosyl moiety have been investigated for the targeted delivery of trans-resveratrol (RSV), a Quorum Sensing Inhibitor (QSI), to Methicillin Resistant Staphylococcus Aureus (MRSA) biofilms.All the glycosylated formulations show a 10-20 % reduction of their hydrodynamic size and a high positive increase in ζ-potential (20÷27mV), with respect to the almost neutral DOPC/Chol liposomes (-3.7 mV). RSV is entrapped in liposomes with high Entrapment Efficiency (EE%), the formulations containing glycosylated amphiphiles showing higher values of EE% (79-90 %) than those containing DOPC/CHOL (65 %). In all the liposomal formulations, the inclusion of RSV causes a decrease in ζ-potential, which is particularly evident in the negative value of DOPC/Chol liposomes (-14.8 mV). This is probably due to the ionization of a small percentage of RSV molecules that point towards the lipid/water interface, as reported in the literature.Greater antioxidant activity is found when RSV is embedded in glycosylated liposomes, rather than DOPC/ CHOL liposomes. This finding suggests a different RSV distribution in the lipid membrane enclosing the glycosylated amphiphiles, which favor an external exposure of RSV.Biological assays carried out to monitor the demolition effect of RSV-loaded liposomes on mature biofilm of MRSA show that the presence of cationic glycoamphiphiles is essential for a demolition effect to take place on the biofilm matrix. In particular, RSV-galactosylated liposomes are the most effective in destroying MRSA biofilm even at a RSV concentration (0.019 mM) sixty times lower than the MIC (1.2 mM). This work demonstrates, for the first time, how the functionalization of liposomes with cationic glycosydic residues can enhance liposome performances as QSI nanocarriers for the treatment of biofilm associated infections.

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