Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a new drug delivery approach to treat peritoneal metastasis. This study evaluated two different devices, one based on aerosolization, the Capnopen ® (CAPNOMED – company) and a second, a prototype named Nebulo ® (GAMIDA - company), based on nebulization. The performance of the two devices were tested for PIPAC distribution and cell penetration of doxorubicin in a sheep model.

Doxorubicin was aerosolized for 30 min, using PIPAC into 6 ewes, 3 with Capnopen ® and 3 with Nebulo ®. The number of doxorubicin positive cells was determined using the ratio between doxorubicin fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei.

DOXO+ nuclei were identified in 46% of the samples. All omental samples, directly localized in front of the nebulizer head, had DOXO+ nuclei except one in the Nebulo group. There was no significant difference in penetration depth between the 2 groups. Concerning the peritoneum, 40% showed by microscope analysis a depth > 100 μm in the Capnopen group, versus 5% in the Nebulo group (p = 0.06).

Our results and limitations observed imposes a change in developing technic. A smaller size of PIPAC droplet is not an efficient option to increase significantly the tissue penetration and concentration of drugs in chemotherapy.