Particle stability and structure on the peritoneal surface in pressurized intra-peritoneal aerosol chemotherapy (PIPAC) analysed by electron microscopy: First evidence of a new physical concept for PIPAC.

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has been introduced to the clinical setting as a novel approach for the treatment of peritoneal metastasis. The local interaction of chemoaerosol droplets with the peritoneal surface as well as their distribution pattern is considered the main advantage over conventional liquid intraperitoneal chemotherapy. The aim of the present study was to investigate the behavior of these aerosol particles during PIPAC application via electron microscopy. Solutions of doxycycline, liposomal doxorubicin and macrophage cells were aerosolized using an established ex-vivo model. PIPAC was performed on peritoneum samples via microcatheter (MC) at a pressure of 12 mmHg C02 at 27°C. Following PIPAC the surface structure of applied particles was measured via electron microscopy. The aerosol particle contact of doxycyclin created a nanofilm of ~200 nm height on the peritoneal surface, and this height was revealed to be independent of the size of the initial particle hitting. These nanofilm blocks of 'cylinders' are of different diameters depending on the initial aerosol particle hitting that spot. Diameters of these 'cylinders' are far wider than the original diameter of the initial aerosol particle. However, coated particles such as liposomal doxorubicin and macrophages remained intact following contact with the peritoneal surface. Based on this and other data, the concept that aerosol particles exhibit a gas-like behavior in the abdomen creating a therapeutic capnoperitoneum should be revised. Fluid aerosol particles collide with the peritoneum creating a nanofilm. The interaction of pressurized intraperitoneal aerosol on the peritoneum is therefore closer to the distribution of a liquid film than to that of a gas. Further studies are required to further analyze the interaction of this nanofilm on the peritoneum.