Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy

Molecular Imaging and Biology volume 15, pages3–11(2013)Cite this article

Abstract

Purpose

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).

Procedures

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.

Results

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.

Conclusions

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.

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Acknowledgments

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.

Author information

Affiliations

  1. Laboratory for Molecular and Functional Imaging: From Physiology to Therapy, FRE 3313–CNRS and University Bordeaux Segalen, 146, rue Léo Saignat, Case 117, 33076, Bordeaux cedex, France

    Marc Derieppe, Anna Yudina, Matthieu Lepetit-Coiffé, Baudouin Denis de Senneville & Chrit Moonen

  2. Imaging Division, University Medical Center Utrecht, Heidelberglaan 100, P.O. Box 85500,, 3508 GA, Utrecht, Netherlands

    Marc Derieppe, Anna Yudina, Clemens Bos & Chrit Moonen

  3. Institut de Mathématiques de Bordeaux, UMR 5251–CNRS–Université Bordeaux 1–INRIA, Bordeaux, France

    Baudouin Denis de Senneville

Authors
  1. Marc Derieppe
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  2. Anna Yudina
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  3. Matthieu Lepetit-Coiffé
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  4. Baudouin Denis de Senneville
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  5. Clemens Bos
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  6. Chrit Moonen
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Corresponding author

Correspondence to Chrit Moonen.

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Derieppe, M., Yudina, A., Lepetit-Coiffé, M. et al. Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy. Mol Imaging Biol 15, 3–11 (2013). https://doi.org/10.1007/s11307-012-0568-9

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Key Words

  • Drug delivery
  • Biological barrier
  • Plasma membrane permeabilization
  • Ultrasound bioeffects
  • Fibered confocal fluorescence microscopy
  • Pharmacokinetic parameters
  • SYTOX Green
  • US-mediated drug delivery