A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel for Intratumoural Injection: An In Vitro and Ex Vivo Assessment of Imaging Characteristics and Material Properties
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.
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.
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.
KeywordsThermoresponsive hydrogel Intratumoural injection Radiopaque Chemotherapy
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.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and Animal Rights
This article does not contain any studies with human participants or animals performed by any of the authors.
For this type of study, informed consent is not required.
Consent for Publication
For this type of study consent for publication is not required.
- 5.Celikoglu F, Celikoglu SI, Goldberg EP. Techniques for intratumoral chemotherapy of lung cancer by bronchoscopic drug delivery. Cancer Ther. 2008;6:545–52.Google Scholar
- 8.Hecht JR, Farrell JJ, Senzer N, Nemunaitis J, Rosemurgy A, Chung T, et al. EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: a phase I/II study. Gastrointest Endosc. 2012;75(2):332–8. https://doi.org/10.1016/j.gie.2011.10.007.CrossRefGoogle Scholar
- 10.DuVall GA, Tarabar D, Seidel RH, Elstad NL, Fowers KD. Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer. Anticancer Drugs. 2009;20(2):89–95. https://doi.org/10.1097/CAD.0b013e3283222c12.CrossRefGoogle Scholar
- 13.Bajpai AK, Shukla SK, Bhanu S, Kankane S. Responsive polymers in controlled drug delivery. Prog Polym Sci. 2008;33(11):1088–118. https://doi.org/10.1016/j.progpolymsci.2008.07.005.CrossRefGoogle Scholar
- 16.Jonsson Comprehensive Cancer Center. Compassionate use of MitoGel in upper tract urothelial carcinoma (NCT02701023). Bethesda (MD): National Library of Medicine (US). 2000–2016. https://clinicaltrials.gov/ct2/show/NCT02701023.. Accessed 02 Mar 2017.
- 17.DeWitt JM, Murthy SK, Ardhanari R, DuVall GA, Wallner G, Litka P, et al. EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial. Gastrointest Endosc. 2016;1:2–3. https://doi.org/10.1016/j.gie.2016.11.017.Google Scholar
- 18.United States Food and Drug Administration. FDA ODAC Briefing Document for NDA 21-236. IntraDose® (cisplatin/epinephrine) Injectable Gel for Recurrent Squamous Cell Carcinoma of the Head and Neck. 2001.Google Scholar
- 24.Kim DY, Kwon DY, Kwon JS, Park JH, Park SH, Oh HJ, et al. Synergistic anti-tumor activity through combinational intratumoral injection of an in situ injectable drug depot. Biomaterials. 2016;85:232–45. https://doi.org/10.1016/j.biomaterials.2016.02.001.CrossRefGoogle Scholar