Hyperthermic pressurized intraperitoneal aerosol drug delivery system in a large animal model: a feasibility and safety study

Abstract

Background: We developed a novel drug delivery system called hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) that hybridized Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). The present study aims to assess the feasibility and safety of HPIPAC system in a large animal survival model.

Methods: Eleven pigs (eight non-survival models and three survival models) were used in the experiment. The heat module in the HPIPAC controller circulates hyperthermic CO₂ in a closed-loop circuit and creates gas-based dry intraperitoneal hyperthermia. Three 12 mm trocars were placed on the abdomen. The afferent CO₂ tube wound with heat generating coil was inserted into a trocar, and the efferent tube was inserted into another trocar. Heated CO₂ was insufflated and circulated in a closed circuit until the intra-abdominal and peritoneal surface temperature reached 42 °C. 100 ml of 5% dextrose in water was nebulized for 5 min and the closed-loop circulation was resumed for 60 min at 42 °C. Tissue biopsies were taken from several sites from the pigs in the survival model.

Results: The average change in core temperature of the pigs was 2.5 ± 0.08 °C. All three pigs displayed no signs of distress, and their vital signs remained stable, with no changes in their diet. In autopsy, inflammatory and fibrotic responses at the biopsy sites were observed without serious pathologic findings.

Conclusions: We successfully proved the feasibility and safety of our novel HPIPAC system in an in-vivo swine survival model.

Keywords: Hyperthermic intraperitoneal chemotherapy; Large animal model; Peritoneal carcinomatosis; Pressurized intraperitoneal aerosol chemotherapy.