Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model

by Selleckchem | Jul 21 2023

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.

Comments:

The experimental study investigated the therapeutic efficacy of a supramolecular hydrogel for drug delivery in the treatment of peritoneal metastases (PM) of colorectal cancer. The hydrogel was designed to provide a local and slow release of the encapsulated drug, either mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC). The aim was to address the limitation of short residence time and subsequent short exposure of cancer cells to the cytostatic agents.

The study used WAG/Rij rats (n = 72) and induced PM by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, the rats received a single intraperitoneal injection of different treatment options: 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).

The primary outcome measured was overall survival, with a maximum follow-up period of 120 days. Intraperitoneal tumor development was monitored non-invasively using bioluminescence imaging. Out of the 72 rats, 61 successfully completed all study procedures and were included in the assessment of therapeutic efficacy.

After 120 days, the overall survival rate in the MMC-loaded hydrogel group was 78%, whereas the free MMC group had a survival rate of 38%. There was a trend toward significance when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087), indicating a potential survival benefit for the MMC-loaded hydrogel group. However, no survival benefit was observed for the cMMC-loaded hydrogel compared to free cMMC.

In conclusion, treating peritoneal metastases with the MMC-loaded hydrogel, which provided prolonged exposure to MMC, showed promising results in terms of improved survival compared to treatment with free MMC alone. This study suggests that the supramolecular hydrogel-based drug delivery system could be an effective approach for enhancing the therapeutic efficacy of intraperitoneal chemotherapy in patients with PM of colorectal cancer. Further research and clinical trials are needed to validate these findings and determine the translational potential of this hydrogel in human patients.