Influence of Lipid Composition on Physicochemical and Antibacterial Properties of Vancomycin-Loaded Nanoscale Liposomes

The bacterial resistance against antibiotics has reached an alarming level, leading to an increase in morbidity and mortality. One of the possible approaches to tackle this problem of major concern for the global community is to renovate "old" antibiotics to make pathogens susceptible to their pharmacological activity. Vancomycin (VAN) is a glycopeptide used for the treatment of Gram-positive bacterial infections such as the ones caused by methicillin-resistant Staphylococcus aureus. Nevertheless, some strains of this bacterium developed high-level VAN resistance. To revert VAN resistance and decrease its side effects, we included this antibiotic in different liposomal formulations. Nanoscaled liposomes were formulated with pure phospholipids differing in the presence of unsaturation and/or in the length of the acyl chains. DPPC liposomes were also tested in a mixture with cholesterol hemisuccinate (at 40 molar percentage) and/or a cationic saturated lipid (at 30 molar percentage) to make them pH-responsible and/or positively charged. Two techniques for liposome preparation, thin film hydration and reverse phase evaporation, were employed and compared. The key element of this investigation is a systematic and rational variation of liposomes composition and VAN loading technique to modulate the physicochemical properties of the formulations. The availability of a "revised" broad-spectrum VAN could increase its therapeutic options in the case of bacterial infections and, at the same time, limit the failure of the treatment due to the beta-lactam resistance in bacteria.