Novel Vancomycin Free Base – Sterosomes for Combating Diseases Caused by Staphylococcus Aureus Infections (S. Aureus and MRSA)

A clarion call to save antibiotics and other antimicrobials is the need for the evolution of novel drug delivery systems to combat resistance posed by Staphylococcus aureus and Methicillin- resistant Staphylococcus aureus (S. aureus and MRSA) to the conventional drug delivery systems. 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 by employing the thin-film hydration method and assessed in terms of their physicochemical, in silico, in vitro and in vivo properties. A preliminary biocompatibility evaluation on MCF-7 and HEK-293 cell lines was also carried out on the VCM-FB – Sterosomes formulation using in vitro cytotoxicity assay. The cytotoxicity results revealed the viability of cell to be above 70% for all the cell lines after exposure to VCM-FB – Sterosomes, therefore indicating its biosafety. VCM-FB – Sterosomes had hydrodynamic diameter (DH), polydispersity index (PDI) and a surface-charge (ζ) of 114.14 ± 0.59 nm, 0.210 ± 0.02 and +36.3 ± 5.42 mV respectively, with an entrapment efficiency (EE%), drug loading capacity (DLC%) and VCM-FB release after 48-hour of 79.61 ± 0.59%, 90.91% w/w and 54.95 ± 9.75% respectively. In silico studies showed VCM-FB – Sterosomes to self-assemble in five nano seconds and was stable thereafter. Stability studies also showed the VCM-FB – Sterosomes formulation to be stable over a period of 90 days while the in vitro haemolytic studies showed VCM-FB – Sterosomes to be non-hemolytic. Interestingly, the VCM-FB – Sterosomes showed 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. Blank Sterosomes were also observed to be effective against these bacteria, with greater effectiveness observed against MRSA. Faster bacterial killing time was also recorded for VCM-FB – Sterosomes compared to bare VCM-FB.Greater damage to the MRSA membrane was indicated by an increase and decrease in electrical conductivity, and protein/DNA concentration, respectively. VCM-FB – Sterosomes were observed to exhibit a superior reduction of matured MRSA biofilm (27.22%) compared to VCM-FB (2.53%). In vivo BALB/c mice-infected skin model showed VCM-FB – Sterosomes to have a more significant MRSA eradication of 27-fold compared to bare VCM-FB, which showed an approximately 4-fold MRSA eradication. The result of this study amplifies the superior efficiency of VCM-FB – Sterosomes for the treatment of S. aureus and MRSA infections compared to conventional form of VCM-FB.