Daniel Göhler1, Veria Khosrawipour2,3, Tanja Khosrawipour3, David Diaz-Carballo4, Thomas Albert Falkenstein3, Jürgen Zieren2, Michael Stintz1, Urs Giger-Pabst5,6. 1. Research Group Mechanical Process Engineering, Institute of Process Engineering and Environmental Technology, Technische Universität Dresden, Dresden, Germany. 2. Department of General Surgery and Therapy Center for Peritonealcarcinomatosis, St. Mary's Hospital Herne, Ruhr University Bochum, Hölkeskampring 40, 44625, Herne, Germany. 3. Basic Research Laboratory Department of Surgery, St. Mary's Hospital Herne, Ruhr University Bochum, Bochum, Germany. 4. Department of Hematology and Medical Oncology, St. Mary's Hospital Herne, Ruhr University Bochum, Bochum, Germany. 5. Department of General Surgery and Therapy Center for Peritonealcarcinomatosis, St. Mary's Hospital Herne, Ruhr University Bochum, Hölkeskampring 40, 44625, Herne, Germany. urs.pabst@marienhospital-herne.de. 6. Basic Research Laboratory Department of Surgery, St. Mary's Hospital Herne, Ruhr University Bochum, Bochum, Germany. urs.pabst@marienhospital-herne.de.
Abstract
BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing. ANALYTICAL METHODS: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated. RESULTS: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm. CONCLUSIONS: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.
BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing. ANALYTICAL METHODS: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated. RESULTS: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm. CONCLUSIONS: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.
Entities:
Keywords:
Aerosol chemotherapy; Aerosol droplet size; Drug distribution pattern; MIP®; PIPAC; Technical construction
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