Treating Colorectal Peritoneal Metastases with an Injectable Cytostatic Loaded Supramolecular Hydrogel in a Rodent Animal Model

Overview

Journal Clin Exp Metastasis

Specialty Oncology

Date 2023 May 21

PMID 37211565

Authors

Anne G W E Wintjens

Hong Liu

Peter-Paul K H Fransen

Kaatje Lenaerts

Geert C van Almen

Marion J Gijbels

Mhamed Hadfoune

Bas T C Boonen

Natasja G Lieuwes

Rianne Biemans

Ludwig J Dubois

Patricia Y W Dankers

Ignace H J T de Hingh

Nicole D Bouvy

Affiliations

Soon will be listed here.

Abstract

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.

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