Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy
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Transport across the plasma membrane is a critical step of drug delivery for weakly permeable compounds with intracellular mode of action. The purpose of this study is to demonstrate real-time monitoring of ultrasound (US)-mediated cell-impermeable model drug uptake with fibered confocal fluorescence microscopy (FCFM).
An in vitro setup was designed to combine a mono-element US transducer, a cell chamber with a monolayer of tumor cells together with SonoVue microbubbles, and a FCFM system. The cell-impermeable intercalating dye, SYTOX Green, was used to monitor US-mediated uptake.
The majority of the cell population showed fluorescence signal enhancement 10 s after US onset. The mean rate constant k of signal enhancement was calculated to be 0.23 ± 0.04 min−1.
Feasibility of real-time monitoring of US-mediated intracellular delivery by FCFM has been demonstrated. The method allowed quantitative assessment of model drug uptake, holding great promise for further local drug delivery studies.
Key WordsDrug delivery Biological barrier Plasma membrane permeabilization Ultrasound bioeffects Fibered confocal fluorescence microscopy Pharmacokinetic parameters SYTOX Green US-mediated drug delivery
We are grateful to Dr. J.R. Cazalets and colleagues (INCIA UMR 5287/University Bordeaux 2, France) for letting us use their cell culture facility. This study was supported by EU project SonoDrugs (FP7-NMP4-LA-2008-213706), ERC project 268906 “Sound Pharma”, and Foundation InNaBioSanté—project ULTRAFITT.
Conflict of interest
The authors declare that they have no conflict of interest.
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