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Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography

  • Research Article
  • Recent Advances in Drug Delivery
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Abstract

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2 weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2 kPa and a loss modulus of about 0.35 kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent.

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Acknowledgements

We thank Dr. Johannes M. Froehlich and Klusapotheke Zürich (Switzerland) for providing Lipiodol. We thank the small animal phenotyping and imaging facility of the CRCHUM for the CT scanner. We thank Mihaela Friciu (UdeM) for technical assistance during particle size analysis, Luca Morsella (UdeM) for assistance with CMC hydrogel formulation, Dr. Junzheng Peng (CRCHUM) for technical assistance during CT experiments, Lim lab (CRCHUM) for providing the mice, and Alexandre Bourgeois (CRCHUM) for assistance during mouse experiments. The graphical abstract, Fig. 2a, and Supplementary Figure 1 were created with Biorender.

Funding

NG gratefully acknowledges scholarships from the Groupe de recherche universitaire sur le médicament at Université de Montréal and the Faculté de Pharmacie at Université de Montréal. Funding from the Natural Science and Engineering Research Council of Canada and the Canada Foundation for Innovation is gratefully acknowledged.

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Authors and Affiliations

  1. Faculté de Pharmacie, Université de Montréal, 2940 Chemin de Polytechnique, Montreal, Québec, H3T 1J4, Canada

    Natalie Guirguis, Yanis Zellagui & Simon Matoori

  2. École Nationale Supérieure de Chimie de Mulhouse, Université de Haute-Alsace, 3 Rue Alfred Werner, 68200, Mulhouse, France

    Yanis Zellagui

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  1. Natalie Guirguis
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Contributions

SM conceptualized and supervised the project. NG and SM contributed to the design of the experiments and writing of the manuscript. NG and YZ conducted the experiments.

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Correspondence to Simon Matoori.

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Communicated by Aliasger Salem

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Guirguis, N., Zellagui, Y. & Matoori, S. Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography. AAPS J 25, 79 (2023). https://doi.org/10.1208/s12248-023-00843-0

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