| Abstrakt: |
A clarion call to save antimicrobials is the need for the evolution of novel delivery systems to combat resistance posed by Staphylococcus aureusand Methicillin-resistant Staphylococcus aureus(S. aureusand 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. aureusand MRSA. VCM-FB – Sterosomes were prepared using the thin-film hydration method and were characterised physiochemically, in silico, in vitroand in vivo. In vitrocytotoxicity 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 silicostudies 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. aureusand 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 vivoBALB/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. aureusand MRSA infection treatment compared to conventional forms. |
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