1. Vancomycin-loaded nanobubbles: A new platform for controlled antibiotic delivery against methicillin-resistant Staphylococcus aureus infections.
- Author
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Argenziano M, Banche G, Luganini A, Finesso N, Allizond V, Gulino GR, Khadjavi A, Spagnolo R, Tullio V, Giribaldi G, Guiot C, Cuffini AM, Prato M, and Cavalli R
- Subjects
- Animals, Cell Line, Cell Survival drug effects, Dextran Sulfate chemistry, Drug Compounding, Drug Liberation, Drug Stability, Fluorocarbons chemistry, Humans, In Vitro Techniques, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus growth & development, Microscopy, Electron, Transmission, Skin metabolism, Skin Absorption, Swine, Ultrasonic Waves, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents radiation effects, Delayed-Action Preparations administration & dosage, Delayed-Action Preparations chemistry, Delayed-Action Preparations radiation effects, Drug Delivery Systems, Nanostructures administration & dosage, Nanostructures chemistry, Nanostructures radiation effects, Nanostructures ultrastructure, Vancomycin administration & dosage, Vancomycin chemistry, Vancomycin radiation effects
- 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 ∼300nm 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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