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

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

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.

MeSH terms

  • Aerosols
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics*
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Infusion Pumps
  • Infusions, Parenteral
  • Swine
  • Tissue Distribution

Substances

  • Aerosols
  • Antibiotics, Antineoplastic
  • Doxorubicin