Vancomycin (Vm) currently represents the gold standard 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 Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by 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. Interestingly, VmLNBs were generally more effective than Vm alone in MRSA killing, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release profile. Besides, VmLNBs were not internalized by staphylococci, opposite to Vm solution. Further US association promoted drug 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 wound infections.

Vancomycin-loaded nanobubbles: A new platform for controlled antibiotic delivery against methicillin-resistant Staphylococcus aureus infections

ARGENZIANO, MONICA
First
;
BANCHE, Giuliana
;
LUGANINI, ANNA;FINESSO, NICOLE;ALLIZOND, Valeria;GULINO, GIULIA ROSSANA;SPAGNOLO, Rita;TULLIO, Viviana Cristina;GIRIBALDI, Giuliana;GUIOT, Caterina;Cuffini, A;PRATO, Mauro
Co-last
;
CAVALLI, Roberta
Co-last
2017-01-01

Abstract

Vancomycin (Vm) currently represents the gold standard 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 Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by 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. Interestingly, VmLNBs were generally more effective than Vm alone in MRSA killing, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release profile. Besides, VmLNBs were not internalized by staphylococci, opposite to Vm solution. Further US association promoted drug 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 wound infections.
2017
523
176
188
Nanobubbles, Vancomycin, Methicillin-resistant Staphylococcus aureus, Ultrasound, Prolonged release
Argenziano, M; Banche, G**; Luganini, A; Finesso, N; Allizond, V; Gulino, Gr; Khadjavid, A; Spagnolo, R; Tullio, V; Giribaldi, G; Guiot, C; Cuffini, A...espandi
File in questo prodotto:
File Dimensione Formato  
IJP-D-16-02774R1.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 1.96 MB
Formato Adobe PDF
1.96 MB Adobe PDF Visualizza/Apri
IJP_Argenziano 2017.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.55 MB
Formato Adobe PDF
2.55 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1634018
Citazioni
  • ???jsp.display-item.citation.pmc??? 20
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 48
social impact