Vancomycin-loaded nanobubbles: A new platform for controlled antibiotic delivery against methicillin-resistant Staphylococcus aureus infections.
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.
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy.
Monica
M
Argenziano
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy. Electronic address: giuliana.banche@unito.it.
Giuliana
G
Banche
Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università degli Studi di Torino, Torino, Italy.
Anna
A
Luganini
Dipartimento di Oncologia, Università degli Studi di Torino, Torino, Italy.
Nicole
N
Finesso
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy.
Valeria
V
Allizond
Dipartimento di Oncologia, Università degli Studi di Torino, Torino, Italy.
Giulia Rossana
GR
Gulino
Dipartimento di Oncologia, Università degli Studi di Torino, Torino, Italy; Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy.
Amina
A
Khadjavi
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy.
Rita
R
Spagnolo
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy.
Vivian
V
Tullio
Dipartimento di Oncologia, Università degli Studi di Torino, Torino, Italy.
Giuliana
G
Giribaldi
Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy.
Caterina
C
Guiot
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy.
Anna Maria
AM
Cuffini
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy; Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy.
Mauro
M
Prato
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy. Electronic address: roberta.cavalli@unito.it.
Roberta
R
Cavalli
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D016264:Dextran Sulfate / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects / Q000648:ultrastructure; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine; D000069453:Ultrasonic Waves; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D010420:Pentanes
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D016264:Dextran Sulfate; D005466:Fluorocarbons; D014640:Vancomycin; C008806:perfluoropentane; D010420:Pentanes
Methicillin-resistant Staphylococcus aureus; Nanobubbles; Prolonged release; Ultrasound; Vancomycin