Technology development of hyperthermic pressurized intraperitoneal aerosol chemotherapy (hPIPAC)

Optimized drug delivery systems are needed for intraperitoneal chemotherapy. The aim of this study was to develop a technology for applying pressurized intraperitoneal aerosol chemotherapy (PIPAC) under hyperthermic conditions (hPIPAC).

This is an ex-vivo study in an inverted bovine urinary bladder (IBUB). Hyperthermia was established using a modified industry-standard device (Humigard). Two entry and one exit ports were placed. Warm-humid CO₂ was insufflated in the IBUB placed in a normothermic bath to simulate body thermal inertia. The temperature of the aerosol, tissue, and water bath was measured in real-time.

Therapeutic hyperthermia (target tissue temperature 41-43 °C) could be established and maintained over 30 min. In the first phase (insufflation phase), tissue hyperthermia was created by insufflating continuously warm-humid CO₂. In the second phase (aerosolization phase), chemotherapeutic drugs were heated up and aerosolized into the IBUB. In a third phase (application phase), hyperthermia was maintained within the therapeutic range using an endoscopic infrared heating device. In a fourth phase, the toxic aerosol was discarded using a closed aerosol waste system (CAWS).

We introduce a simple and effective technology for hPIPAC. hPIPAC is feasible in an ex-vivo model by using a combination of industry-standard medical devices after modification. Potential pharmacological and biological advantages of hPIPAC over PIPAC should now be evaluated.