Mannosyl, glucosyl or galactosyl liposomes to improve resveratrol efficacy against Methicillin Resistant Staphylococcus aureus biofilm

Abstract

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.

Toxicity Assessment of Resveratrol Liposomes-in-Hydrogel Delivery System by EpiVaginalTM Tissue Model

“…The natural polyphenol RES has been shown to act as a potent antioxidant [7,9] and has demonstrated multiple beneficial effects, including as an antimicrobial [9,10,12] and anti-biofilm agent [41,42]. Hence, RES is a promising candidate as novel antimicrobial agent in the treatment of infections, including localized therapy of vaginal infections.…”

Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor

“…Furthermore, surface decoration of nanocarriers with ligands, e.g., carbohydrates, antibodies, peptides, and proteins, allows for selective cell-receptor-mediated targeting [15,61], leading to high local concentrations and enabling penetration through biobarriers [14,38]. For example, the surface functionalization of resveratrol-loaded liposomes with cationic glyco-amphiphiles (galactosyl) was recently shown to increase the antibiotic efficacy of the quorum-sensing inhibitor against MRSA-biofilm with a 60-fold reduction in MIC compared to free resveratrol [62].…”

Resveratrol and Resveratrol-Loaded Galactosylated Liposomes: Anti-Adherence and Cell Wall Damage Effects on Staphylococcus aureus and MRSA

“…In fact, not only are different Minimal Inhibitory Concentration (MIC) values reported but, also, in some experiments, no antibacterial activity is even found. Regarding the anti-biofilm activity, we are faced with the same scenario: some authors report that RSV does not inhibit S. aureus biofilm formation [9,11], others report that it reduces the ability of S. aureus to form biofilm and that it is able to disrupt mature biofilms [12,13]. Also, in the case of biofilm, it is unclear whether RSV anti-biofilm activity is attributable to its anti-adhesive or bacterial-growth-inhibiting properties.…”

“…RSV was embedded in liposomes formulated with a natural phospholipid (1,2-dioleoylsn-glycero-3-phosphocholine, DOPC) and cholesterol (Chol), in the presence and in the absence of a cationic galactosylated amphiphile, GLT1, that has been already proven to enhance RSV-loaded liposome activity in the demolition experiments of mature MRSA biofilm [13,22] (Figure 1).…”