Intraperitoneal administration of a thermogel combined with an anticancer agent for the prevention of peritoneal carcinomatosis in a pig model.

Abstract

Background: Surgeons may discover perioperative clinical situations associated with an increased risk of peritoneal carcinomatosis recurrence after primary resection. We developed a thermogel that can be used as a drug carrier to deliver an anticancer agent in the peritoneal cavity as a rescue solution. The spatial distribution of the thermogel and pharmacokinetics of chemotherapy have been studied in pigs. The safety of the thermogel was assessed based on the healing of bowel sutures.

Methods: Nine pigs received gel with oxaliplatin at 130 mg/200 mL (TG-Ox group), and 4 pigs received the gel alone (TG group). Digestive tract and bladder wounds were made and sutured. Pigs were sacrificed at different times after surgery to monitor the distribution of the thermogel and to detect the occurrence of bowel fistulas. Oxaliplatin plasma and tissue concentrations were determined via mass spectrometry.

Results: After 3 h, 100 % of the regions of interest were covered by the gel, 78 % were covered after 2 days, and 38 % were covered after 4 days. The thermogel delayed the release of oxaliplatin into the systemic circulation and significantly prolonged tissue impregnation. Anastomotic fistulas were observed in the TG-Ox group (10 %) versus 0 % in the TG group (p = 0.31).

Conclusions: A homogeneous distribution of the thermogel throughout the peritoneal cavity was observed, and the thermogel fulfilled its functions as a drug carrier, including ensuring safety and delaying chemotherapy delivery. Treatment-induced toxicity due to oxaliplatin was identified. The concept of a rescue solution being available in operating rooms was demonstrated.