Evaluating the Effect of Micropump© Position, Internal Pressure and Doxorubicin Dosage on Efficacy of Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model
| Autor: | Jürgen Zieren, David Diaz-Carballo, Veria Khosrawipour, Irenäus A. Adamietz, Aras Osma, Tanja Khosrawipour, Thomas Albert Falkenstein, Eckart Förster, Khashayar Fakhrian |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Materials science Swine medicine.medical_treatment Micropump Pharmacology In Vitro Techniques 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems medicine Pressure Animals Doxorubicin Penetration depth Peritoneal Neoplasms Aerosols Chemotherapy Carcinoma Internal pressure General Medicine Penetration (firestop) Aerosol 030104 developmental biology Oncology Microscopy Fluorescence 030220 oncology & carcinogenesis Laparoscopy Peritoneum Ex vivo medicine.drug Biomedical engineering |
| Zdroj: | Anticancer research. 36(9) |
| ISSN: | 1791-7530 |
| Popis: | BACKGROUND/AIM Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel clinical approach to the treatment of peritoneal carcinomatosis. A well-established, not anatomic ex vivo PIPAC model was used to investigate the influence of changes in internal pressure, distance of the Micropump(©) (MIP) to the distributing surface and the drug concentration on the penetration depth of doxorubicin in the target tissue. MATERIALS AND METHODS Doxorubicin was aerosolized in an ex vivo PIPAC model using a hermetic container system mimicking the abdominal cavity. Fresh post-mortem swine peritoneum was cut into proportional samples. Tissue specimens were spatially placed at 4 different spots within the box: P1, on the distributing surface of the box, directly opposite to MIP; P2, on the side wall of the box; P3, on the ceiling of the box; P4, on the distributing surface with a partial cover. Impact of changes in the following parameters were analyzed and compared with clinically established values (CEVs) at our center: pressure (CEV=12 mmHg), distance of the MIP from the distributing surface (CEV=8 cm) and doxorubicin concentration (CEV=3 mg/50 ml). In-tissue doxorubicin penetration depth was measured using fluorescence microscopy on frozen thin sections. RESULTS Tissue positioning in the box had a significant impact on drug penetration after PIPAC with CEV. Under CEV conditions, the highest drug penetration depth was observed in the tissue placed on the distributing surface directly opposite to the MIP (P1: 351 μm, P2: 77 μm, P3: 66 μm, P4: 34 μm). A closer positioning of the MIP lead to a significantly higher mean depth penetration of doxorubicin in the P1 in contrast to other samples in which a reduced drug penetration was observed (1 cm vs. 8 cm distance from MIP to the distributing surface, P1 at 1 cm: 469 μm vs. P1 at 8 cm: 351 μm, p |
| Databáze: | OpenAIRE |
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