Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous drug distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial drug distribution pattern of PIPAC has not been investigated in detail. Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 A degrees C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 +/- A 79 A mu m) compared with the side wall (C: 77 +/- A 18 A mu m; p < 0.01) and the top of the box (D: 65 +/- A 17 A mu m; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 +/- A 19 A mu m; p < 0.001). The study data suggest that the spatial drug distribution pattern of ex vivo PIPAC is heterogeneous.