Vancomycin-loaded dextran sulfate-shelled/perfluoropentane-cored nanobubbles for antibiotic transdermal delivery

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