PEG-grafted liposomes for enhanced antibacterial and antibiotic activities: An in vivo study

Abstract

Staphylococcus aureus (S. aureus) biofilm-associated infections are a primary concern for public health worldwide. Current therapeutics cannot penetrate the biofilms efficiently, resulting in low drug concentrations at the infected sites and increasing the frequency of drug usage. To solve this issue, nanotechnology platforms seem to be a promising approach. In this study, the potential therapeutic effects of (PEG)ylated liposome (PEG-Lip) for the delivery of nafcillin (NF) antibiotic were assessed. The results demonstrated that NF-loaded liposome (Lip-NF) and NF-loaded PEG-Lip (PEG-Lip-NF) released 76.4 and 62% of the loaded NF, respectively, in a controlled manner after 50 h. Also, it was found that PEG-Lip-NF, compared to Lip-NF and NF, was more effective against a methicillin-susceptible S. aureus (MSSA; minimum inhibitory concentration (MIC): 1.0 ± 0.03, 0.5 ± 0.02, and 0.25 ± 0.01 μg/mL; and minimum biofilm inhibitory concentration (MBIC₅₀): 4.0 ± 0.18, 1.0 ± 0.04, and 0.5 ± 0.02 μg/mL for NF, Lip-NF, and PEG-Lip-NF, respectively). PEG-Lip-NF, compared to NF and Lip-NF, could also more efficiently decrease the side effects of NF through improving human MG-63 osteoblast cell viability (cell viability at 100 μM of NF: 76, 68, and 38% for PEG-Lip-NF, Lip-NF, and NF, respectively). PEG-Lip-NF, compared to control, NF, and Lip-NF groups, was more efficacious by 45, 25, and 10%, respectively, to decrease the virulence of MSSA bacteremia through inhibiting the weight loss of the infected mice. Also, PEG-Lip-NF and Lip-NF, compared to control and NF groups, caused a considerable decrease in the mortality rate in a murine model of bacteremia (number of dead mice: 0, 0, 2, and 8 out of 15 for PEG-Lip-NF, Lip-NF, NF, and control groups, respectively). Overall, the results of this study demonstrated that the loading of NF into PEG-Lip is a promising strategy to decrease the side effects of NF with improved antibacterial effects for the treatment of MSSA biofilm-associated infections.

Keywords: Antibiotic; Biofilm-associated infections; Drug delivery; Methicillin-sensitive staphylococcus aureus; Nafcillin; PEGylated liposome.