Novel vancomycin free base – Sterosomes for combating diseases caused by Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus infections (S. Aureus and MRSA)

Abstract

A clarion call to save antimicrobials is the need for the evolution of novel delivery systems to combat resistance posed by Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (S. aureus and MRSA) to conventional forms. Herein, we present a novel vancomycin free base – sterosomes (VCM-FB – Sterosomes) for vancomycin free base (VCM-FB) delivery against S. aureus and MRSA. VCM-FB – Sterosomes were prepared using the thin-film hydration method and were characterised physiochemically, in silico, in vitro and in vivo. In vitro cytotoxicity on MCF-7 and HEK-293 cell lines were evaluated, with results revealing cell viability above 70% after exposure to VCM-FB – Sterosomes, indicating biosafety. VCM-FB – Sterosomes had a hydrodynamic diameter, polydispersity index and surface-charge of 114.14 ± 0.59 nm, 0.210 ± 0.02 and +36.3 ± 5.42 mV, respectively, with entrapment efficiency, drug loading and VCM-FB release after 48 h of 79.61 ± 0.59%, 90.91% w/w and 54.95 ± 9.75% respectively. In silico studies showed a self-assembly in five nano seconds, which was stable thereafter. VCM-FB – Sterosomes were seen to be stable over 90 days and were also non-hemolytic. VCM-FB – Sterosomes showed a 2-fold superior minimum inhibition efficiency (MIC) against S. aureus and MRSA, relative to bare VCM-FB, with MICs of 1.95 μg/mL and 0.98 μg/mL for VCM-FB and VCM-FB – Sterosomes (S. aureus), and 7.81 μg/mL and 3.91 μg/mL for VCM-FB and VCM-FB – Sterosomes (MRSA), respectively. A faster bacterial killing time was also recorded for VCM-FB – Sterosomes compared to bare VCM-FB. Greater MRSA membrane damage was indicated by an increase and decrease in electrical conductivity, and protein/DNA concentration, respectively. VCM-FB – Sterosomes showed superior MRSA biofilm reduction (27.22%) compared to VCM-FB (2.53%). In vivo BALB/c mice-infected skin model showed that VCM-FB – Sterosomes had significant MRSA eradication (27-fold) compared to bare VCM-FB (4-fold). These results amplify the superiority of VCM-FB – Sterosomes for S. aureus and MRSA infection treatment compared to conventional forms.