Resveratrol-loaded glycosylated liposomes for targeting bacteria

Biofilm-associated bacterial diseases are a major health problem due to the high antibiotic resistance of biofilm infections. In recent years, several methods, some of which relying on nanotechnology, have been developed to tackle this problem. The search for non-antibiotic strategies has renewed interest in natural molecules that exploit alternative bacterial-fighting mechanisms and, above all, do not induce resistance. In this context, we have developed two sets of cationic glycosylated liposomes for the targeted delivery of trans-resveratrol (RSV), a secondary plant metabolite with antimicrobial properties, to bacteria that express carbohydrate-specific proteins able to recognize monosaccharides, namely Staphylococcus epidermidis and Methicillin Resistant Staphylococcus Aureus (MRSA). Liposome physico-chemical properties (diameter, PDI, charge, RSV entrapment efficiency) were measured by DLS, electrophoretic mobility, and HPLC.

Liposomes used in the experiments on MRSA were composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine, cholesterol (Chol) and glycoamphiphiles featuring a galactosyl, mannosyl or glucosyl moiety. The objective was to identify the best sugar moiety to target MRSA biofilm. Microbiological tests carried out to monitor the demolition effect of RSV-loaded liposome on MRSA mature biofilm showed that RSV-galactosylated liposomes are the most effective at a RSV concentration sixty times below the MIC.

Liposomes used in the experiments on S. epidermidis were formulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, Chol, and the glycoamphiphile featuring the glucose residue. The ability of RSV-loaded liposomes to inhibit the growth of a slime positive and a slime negative strain of S. epidermidis was evaluated. Glucosylated liposomes, non-toxic in itself, kill bacteria at concentration tenfold under the MIC of RSV.