Targeting pharmaceuticals through the endothelial barrier is crucial for drug delivery. In this context, cavitation‐assisted permeation shows promise for effective and reversible opening of intercellular junctions. A vessel‐on‐a‐chip is exploited to investigate and quantify the effect of ultrasound‐excited microbubbles—stable cavitation—on endothelial integrity. In the vessel‐on‐a‐chip, the endothelial cells form a complete lumen under physiological shear stress, resulting in intercellular junctions that exhibit barrier functionality. Immunofluorescence microscopy is exploited to monitor vascular integrity following vascular endothelial cadherin staining. It is shown that microbubbles amplify the ultrasound effect, leading to the formation of interendothelial gaps that cause barrier permeabilization. The total gap area significantly increases with pressure amplitude compared to the control. Gap opening is fully reversible with gap area distribution returning to the control levels 45 min after insonication. The proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation‐enhanced endothelium permeability and shows potential for validating irradiation protocols for in vivo applications.

Reversible cavitation-induced junctional opening in an artificial endothelial layer / Silvani, Giulia; Scognamiglio, Chiara; Caprini, Davide; Marino, Luca; Chinappi, Mauro; Sinibaldi, Giorgia; Peruzzi, Giovanna; Kiani, Mohammad F.; Casciola, Carlo Massimo. - In: SMALL. - ISSN 1613-6810. - (2019). [10.1002/smll.201905375]

Reversible cavitation-induced junctional opening in an artificial endothelial layer

Giulia Silvani
Primo
;
Davide Caprini;Luca Marino;Giorgia Sinibaldi;Carlo Massimo Casciola
Ultimo
2019

Abstract

Targeting pharmaceuticals through the endothelial barrier is crucial for drug delivery. In this context, cavitation‐assisted permeation shows promise for effective and reversible opening of intercellular junctions. A vessel‐on‐a‐chip is exploited to investigate and quantify the effect of ultrasound‐excited microbubbles—stable cavitation—on endothelial integrity. In the vessel‐on‐a‐chip, the endothelial cells form a complete lumen under physiological shear stress, resulting in intercellular junctions that exhibit barrier functionality. Immunofluorescence microscopy is exploited to monitor vascular integrity following vascular endothelial cadherin staining. It is shown that microbubbles amplify the ultrasound effect, leading to the formation of interendothelial gaps that cause barrier permeabilization. The total gap area significantly increases with pressure amplitude compared to the control. Gap opening is fully reversible with gap area distribution returning to the control levels 45 min after insonication. The proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation‐enhanced endothelium permeability and shows potential for validating irradiation protocols for in vivo applications.
2019
cavitation; drug delivery; endothelial junctions; permeabilization; vessel‐on‐a‐chip
01 Pubblicazione su rivista::01a Articolo in rivista
Reversible cavitation-induced junctional opening in an artificial endothelial layer / Silvani, Giulia; Scognamiglio, Chiara; Caprini, Davide; Marino, Luca; Chinappi, Mauro; Sinibaldi, Giorgia; Peruzzi, Giovanna; Kiani, Mohammad F.; Casciola, Carlo Massimo. - In: SMALL. - ISSN 1613-6810. - (2019). [10.1002/smll.201905375]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1333705
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