Vancomycin-loaded dextran sulfate/perfluoropentane nanobubbles for controlled drug release against methicillin-resistant Staphylococcus aureus infections.

Vancomycin (Vm) currently represents the main stay against methicillin-resistant Staphylococcus aureus (MRSA) infections [1]. However, Vm is associated with low oral bioavailability, formulation stability issues, and severe side effects upon systemic administration [2]. These drawbacks could be overcome by Vm topical administration when properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug transdermal delivery [3-5]. In this work, perfluoropentane-cored NBs were functionalized through Vm coupling to the outer dextran sulfate shell. Vm-loaded NBs (VmLNBs) displayed ~300 nm sizes, anionic surfaces and good drug encapsulation efficiency. In vitro, VmLNBs showed prolonged drug release kinetics, not accompanied by cytotoxicity on human keratinocytes. Opposite to carrier-free Vm, VmLNBs were not internalized by S. aureus cells. Nevertheless, VmLNBs were as effective in killing MRSA as Vm alone, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release. Further US administration promoted drug transdermal delivery from VmLNBs through an in vitro model of porcine skin. Taken together, these results support the hypothesis that proper Vm encapsulation in US-responsive NBs might be a promising strategy for the topical treatment of MRSA infections.