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. 2021 Dec;28(1):1179-1187.
doi: 10.1080/10717544.2021.1937382.

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

Soo Jin Park  1 , Eun Ji Lee  1 , Hee Su Lee  2 , Junsik Kim  2 , Sunwoo Park  3 , Jiyeon Ham  3 , Jaehee Mun  1 , Haerin Paik  1 , Hyunji Lim  1 , Aeran Seol  1 , Ga Won Yim  4 , Seung-Hyuk Shim  5 , Beong-Cheol Kang  6 , Suk Joon Chang  7 , Whasun Lim  8 , Gwonhwa Song  3 , Jae-Weon Kim  1 , Nara Lee  9 , Ji Won Park  10 , Jung Chan Lee  11   12 , Hee Seung Kim  1 ; KoRIA* trial group
Affiliations

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

Soo Jin Park et al. Drug Deliv. 2021 Dec.

Abstract

This study aims to evaluate the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Because relevant medical devices have not been introduced, we developed our prototype of pressurized intraperitoneal aerosol chemotherapy (PIPAC) and RIPAC by adding a conical pendulum motion device for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate the drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate the tissue concentrations and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via 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, and capnoperitoneum of 12 mmHg was maintained for 30 min. As a result, RIPAC showed a wider distribution and stronger intensity than PIPAC. Compared with PIPAC, RIPAC demonstrated high values of the tissue concentration in the central, right upper, epigastrium, left upper, left lower, right lower, and right flank regions (median, 375.5-2124.9 vs. 161.7-1240 ng/ml; p ≤ .05), and higher values of the depth of concentrated diffusion and depth of maximal diffusion (median, 232.5-392.7 vs. 116.9-240.1 μm; 291.2-551.2 vs. 250.5-362.4 μm; p ≤ .05) in all regions except for bowels. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no related toxicities. Conclusively, RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.

Keywords: Intraperitoneal chemotherapy; doxorubicin; drug delivery; peritoneal metastasis; pharmacokinetics.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Schematic diagram of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC). (A) A high-pressure injector to generate a pressure of 7 bars (=101 psi), (B) the conical pendulum motion device for rotating the nozzle during RIPAC, and (C) the spraying angle of 77.2 degrees.
Figure 2.
Figure 2.
Comparison of the distribution and intensity of 1% methylene blue staining in pressurized intraperitoneal aerosol chemotherapy (PIPAC), and rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in (A) the parietal and (B) visceral peritoneum.
Figure 3.
Figure 3.
Comparison of tissue concentrations of doxorubicin between pressurized intraperitoneal aerosol chemotherapy (PIPAC) and rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) according to the modified Peritoneal Cancer Index (*p ≤ .05).
Figure 4.
Figure 4.
The depth of concentrated diffusion (DCD) and the depth of maximal diffusion (DMD) using confocal laser scanning microscopy in pressurized intraperitoneal aerosol chemotherapy (PIPAC) and rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) according to the modified Peritoneal Cancer Index.
Figure 5.
Figure 5.
Comparison of the depth of concentrated diffusion (DCD) and the depth of maximal diffusion (DMD) between pressurized intraperitoneal aerosol chemotherapy (PIPAC) and rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) according to the modified Peritoneal Cancer Index (*p ≤ .05).
Figure 6.
Figure 6.
The pharmacokinetic properties of doxorubicin after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC). (A) Individual data and (B) group data.
See this image and copyright information in PMC

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