Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm

Abstract

<b>Objective:</b> The aim of the present study was to encapsulate vancomycin in different liposomal formulations and compare the <i>in vitro</i> antimicrobial activity against <i>Staphylococcus aureus</i> biofilms. <b>Methods:</b> Large unilamellar vesicles of conventional (LUV VAN), fusogenic (LUV_fuso VAN), and cationic (LUV_cat VAN) liposomes encapsulating VAN were characterized in terms of size, polydispersity index, zeta potential, morphology, encapsulation efficiency (%EE) and <i>in vitro</i> release kinetics. The formulations were tested for their Minimum Inhibitory Concentration (MIC) and inhibitory activity on biofilm formation and viability, using methicillin-susceptible <i>S. aureus</i> ATCC 29213 and methicillin-resistant <i>S. aureus</i> ATCC 43300 strains. <b>Key Findings:</b> LUV VAN showed better %EE (32.5%) and sustained release than LUV_fuso VAN, LUV_cat VAN, and free VAN. The formulations were stable over 180 days at 4°C, except for LUV VAN, which was stable up to 120 days. The MIC values for liposomal formulations and free VAN ranged from 0.78 to 1.56 µg/ml against both tested strains, with no difference in the inhibition of biofilm formation as compared to free VAN. However, when treating mature biofilm, encapsulated LUV_fuso VAN increased the antimicrobial efficacy as compared to the other liposomal formulations and to free VAN, demonstrating a better ability to penetrate the biofilm. <b>Conclusion:</b> Vancomycin encapsulated in fusogenic liposomes demonstrated enhanced antimicrobial activity against mature <i>S. aureus</i> biofilms.