Evaluation of a Novel Prototype for Pressurized Intraperitoneal Aerosol Chemotherapy

Abstract

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been suggested as an alternative option for treating peritoneal carcinomatosis (PC). Even with its clinical advantages, the current PIPAC system still suffers from limitations regarding drug distribution area and penetration depth. Thus, we evaluated the new PIPAC system using a novel prototype, and compared its performance to the results from previous studies related with the current MIP® indirectly because the system is currently not available for purchase in the market. The developed prototype includes a syringe pump, a nozzle, and controllers. Drug distribution was conducted using a methylene blue solution for performance test. For penetration depth evaluation, an ex-vivo experiment was performed with porcine tissues in a 3.5 L plastic box. Doxorubicin was sprayed using the novel prototype, and its penetration depth was investigated by confocal laser scanning microscopy. The experiment was repeated with varying nozzle levels from the bottom. The novel prototype sprays approximately 30 μm drug droplets at a flow rate of 30 mL/min with 7 bars of pressure. The average diameter of sprayed region with concentrated dye was 18.5 ± 1.2 cm, which was comparable to that of the current MIP® (about 10 cm). The depth of concentrated diffusion (DCD) did not differ among varying nozzle levels, whereas the depth of maximal diffusion (DMD) decreased with increasing distance between the prototype and the bottom (mean values, 515.3 μm at 2 cm; 437.6 μm at 4 cm; 363.2 μm at 8 cm), which was comparable to those of the current MIP® (about 350–500 μm). We developed a novel prototype that generate small droplets for drug aerosolization and that have a comparably wide sprayed area and depth of penetration to the current MIP® at a lower pressure.

Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum

“…For delivering doxorubicin as aerosols, we used our prototype for PIPAC, which sprayed approximately 30-µm sized droplets through the nozzle, DreamPen ® (Dalim Biotech, Gangwon, South Korea), with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars equivalent to about 100 psi (Lee et al., 2020 ). The mean diameter of the sprayed region was 18.5 cm, and the penetration depth ranged from 360 to 520 µm, comparable to previous studies using the microinjection pump (Capnopen ® ; Capnomed, Villingendorf, Germany) (Khosrawipour et al., 2016b ; Gohler et al., 2017 ).…”

Rotational intraperitoneal pressurized aerosol chemotherapy in a porcine model

“…For PIPAC, the nebulizer was inserted into a 12-mm bladeless trocar, and 1% methylene blue of 150 mL was nebulized at 30 mL/min over a few seconds in the room temperature by the syringe pump which we developed previously (20 ℃) (18), and the abdominal pressure was maintained at 12 mmHg for 30 minutes. The aerosol was eliminated using a pressure-limited waste system including filter.…”

Development of Rotational Intraperitoneal Pressurized Aerosol Chemotherapy to Enhance Drug Delivery into the Peritoneum

“…For delivering doxorubicin as aerosols, we used our prototype for PIPAC, which sprayed approximately 30µm sized droplets through the nozzle with a velocity of 5 km/h at a ow rate of 30 ml/min under a pressure of 7 bars equivalent to about 100 psi [18]. The mean diameter of the sprayed region was 18.5 cm, and the penetration depth ranged from 360 to 520 µm, comparable to previous studies using the microinjection pump (Capnopen®; Capnomed, Villingendorf, Germany) [19,20].…”

“…First of all, RIPAC was superior to EPIC and PIPAC in terms of the distribution and intensity of the chemotherapeutic agents. Even though aerosols with a median diameter of 25 µm are injected into the peritoneal cavity with a velocity of 60 km/hr in PIPAC [29], RIPAC may spray droplets with a median diameter of 30 µm with a velocity of 5 km/hr under the same ow rate of 30 ml/min [18]. This means that the nozzle injection outlet may be larger in RIPAC than in PIPAC, which can reduce the turbulent ow of aerosols with a lower velocity in RIPAC [30].…”

“…In particular, it is important that the DCD was higher in RIPAC than in PIPAC because the area with a concentrated population of cells affected by doxorubicin can promote cytotoxic effects [18]. Moreover, the DMD after PIPAC in this study was similar to the value reported in a previous study (≤ 400 µm), 28 and RIPAC showed a higher DMD than PIPAC (≤ 500 µm) in most of the regions in the peritoneal cavity, indicating that RIPAC may be more advantageous for the passive diffusion of chemotherapeutic agents than PIPAC.…”