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. 2016 Nov;142(11):2275-80.
doi: 10.1007/s00432-016-2234-0. Epub 2016 Sep 2.

Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model

Veria Khosrawipour  1   2 , Tanja Khosrawipour  3   4 , Alexander Jens Peter Kern  4 , Aras Osma  4 , Burak Kabakci  4 , David Diaz-Carballo  4 , Eckart Förster  5 , Jürgen Zieren  3 , Khashayar Fakhrian  6
Affiliations

Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model

Veria Khosrawipour et al. J Cancer Res Clin Oncol. 2016 Nov.

Abstract

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach delivering intraperitoneal chemotherapy by means of a pressurized aerosol. This study was conducted to evaluate the distribution pattern of doxorubicin in the abdominal cavity after PIPAC in a postmortem swine model.

Methods: Doxorubicin was aerosolized through a Micropump© (MIP) into the peritoneal cavity of two swines at a pressure of 12 mm Hg CO2 and 32 °C. To measure the distribution of the drug, 9 different positions within the abdominal cavity were sampled. In-tissue doxorubicin penetration was evaluated using fluorescence microscopy on frozen thin sections.

Results: A maximum of drug penetration was observed in the area around the MIP. The penetration in the small intestine reached a depth of 349 ± 65 µm. Penetration depth in the right upper abdomen and left upper abdomen were 349 ± 65 and 140 µm ± 26 µm, respectively. Distant areas to the MIP showed variable penetration rates between 50 and 150 µm.

Conclusions: Doxorubicin reached all areas within the peritoneum. Highest penetration rates were measured in the area around the Micropump. Further studies are warranted to evaluate and optimize the distribution and penetration of cytotoxic agent into the tissue after PIPAC.

Keywords: Ex vivo swine; Intraperitoneal chemotherapy; PIPAC; Peritoneal carcinomatosis; Whole abdominal radiation.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
PIPAC performed on a postmortem swine. A High-pressure injector. B Micropump
Fig. 2
Fig. 2
Microscopic analysis (Magnification: 20×) of penetration depth of doxorubicin in local peritoneal tissue samples of fresh of German land race pigs. Nuclei (blue) are stained with 4′,6-diamidino-2-phenylindole (DAPI). a Right upper abdomen; b epigastric area; c right subdiaphragmal area, d left subdiaphragmal area; e left upper abdomen; f left lower abdomen; g right lower abdomen; h stomach; and i small intestine
Fig. 3
Fig. 3
Doxorubicin penetration in µm at different areas in the abdomen red (swine one) and blue (swine two)
See this image and copyright information in PMC

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