Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms

Abstract

Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.

Moxifloxacin Liposomes: Effect of Liposome Preparation Method on Physicochemical Properties and Antimicrobial Activity against Staphylococcus epidermidis

“…Several other reports have also proved in vitro and in vivo (in some cases) the superior anti-biofilm activity of liposomal drugs. It was indeed proposed that the reduced penetra-tion of antibiotics through biofilm and low accumulation at infected sites can be overcome by nanotechnological platform approaches [53]. In this context, cationic liposomes were found to have a high anti-biofilm effect and prolonged retention on P. aeruginosa biofilm, and anionic liposomes showed high permeability in the biofilms.…”

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

“…If the biofilm involves a multidrug-resistant strain such as methicillin resistant Staphylococcus aureus (MRSA), the infection may become chronic and even untreatable. Nevertheless, in vitro and in vivo studies have demonstrated improved efficacy of liposomal formulations against biofilm associated MRSA infections [69,103,104]. In particular, a liposomal formulation co-loaded with vancomycin and ciprofloxacin allowed complete sterilization of the bone in a S. aureus osteomyelitis model, showing this strategy has high therapeutic potential against these life-threatening infections [105].…”

The Two Weapons against Bacterial Biofilms: Detection and Treatment

“…As shown in several studies, nanoscale size allows for the nanoparticles to penetrate microbial cell walls and biofilms layers, causing several events such as irreversible damage of microbial membranes [ 9 , 117 , 118 ]. Several hypotheses for nanoparticles mechanisms of action have been explored, including cell membrane alterations and disruption [ 119 , 120 ], ROS generation, and lipid peroxidation [ 121 , 122 , 123 ].…”

“…This increased resistance can be attributed to different factors, including decreased diffusion of antimicrobial agents through the self-produced extracellular matrix (made of polysaccharides, nucleic acids, and proteins matrix) [ 8 , 9 , 10 ], altered metabolic activity, and formation of persister cells [ 11 ]. Moreover, a relevant characteristic of biofilms is the fact that bacteria are able to inter-communicate and collaborate to survive in even the hardest conditions.…”