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A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel for Intratumoural Injection: An In Vitro and Ex Vivo Assessment of Imaging Characteristics and Material Properties

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Abstract

Purpose

Thermoresponsive hydrogels are gels which have different properties at varying temperatures. The objective of this study was to assess the material characteristics, imaging properties and chemotherapeutic drug release profile of a novel radiopaque thermoresponsive hydrogel in vitro, which is liquid at room temperature but solidifies at body temperature, to determine potential suitability for intratumoural delivery.

Materials and Methods

An iodinated radiopaque thermoresponsive hydrogel was formulated using iodixanol at a range of concentrations and assessed for sol–gel transition, radiopacity and imaging using CT and US. A lead formulation containing iodixanol at a concentration of 9.22% weight by weight (w/w, g of iodixanol per g of hydrogel) was evaluated in vitro for injectability, disintegration and dual drug release of cisplatin and paclitaxel from the hydrogel formulation.

Results

Radiopacity of the hydrogel increased in a concentration-dependent manner, but the highest concentration of iodixanol evaluated in this study (13.83% w/w) adversely affected the sol–gel transition of the hydrogel; therefore, 9.22% w/w iodixanol hydrogel was identified as the lead formulation. This formulation was readily visible on both CT and US. The formulation was hand injectable through a range of clinically relevant devices, had a sustained disintegration profile for up to 28 days and was able to deliver a sustained release of chemotherapeutic drug for up to 10 days.

Conclusions

Favourable in vitro and ex vivo imaging and material characteristics of this thermoresponsive gel are demonstrated, suggesting potential interventional oncology applications for image-guided intratumoural delivery of sustained-release chemotherapy.

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Funding

This study was funded by an Enterprise Ireland Commercialisation Fund (CF-2016-0431P) and a Royal College of Surgeons in Ireland School of Pharmacy bursary.

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Authors and Affiliations

  1. School of Pharmacy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephen’s Green, Dublin 2, Ireland

    Seóna M. Rossi & Helena M. Kelly

  2. Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland

    Seóna M. Rossi & Helena M. Kelly

  3. Department of Radiology, Beaumont Hospital, Dublin 9, Ireland

    Timothy E. Murray & Michael J. Lee

  4. School of Chemical and Pharmaceutical Sciences, Dublin Institute of Technology, Dublin 2, Ireland

    John Cassidy

Authors
  1. Seóna M. Rossi
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  2. Timothy E. Murray
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  5. Helena M. Kelly
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Correspondence to Helena M. Kelly.

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Rossi, S.M., Murray, T.E., Cassidy, J. et al. A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel for Intratumoural Injection: An In Vitro and Ex Vivo Assessment of Imaging Characteristics and Material Properties. Cardiovasc Intervent Radiol 42, 289–297 (2019). https://doi.org/10.1007/s00270-018-2103-0

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  • DOI: https://doi.org/10.1007/s00270-018-2103-0

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