TY - JOUR
T1 - Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum
AU - On behalf of the KoRIA trial group
AU - Park, Soo Jin
AU - Lee, Eun Ji
AU - Lee, Hee Su
AU - Kim, Junsik
AU - Park, Sunwoo
AU - Ham, Jiyeon
AU - Mun, Jaehee
AU - Paik, Haerin
AU - Lim, Hyunji
AU - Seol, Aeran
AU - Yim, Ga Won
AU - Shim, Seung Hyuk
AU - Kang, Beong Cheol
AU - Chang, Suk Joon
AU - Lim, Whasun
AU - Song, Gwonhwa
AU - Kim, Jae Weon
AU - Lee, Nara
AU - Park, Ji Won
AU - Lee, Jung Chan
AU - Kim, Hee Seung
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Intraperitoneal chemotherapy
KW - doxorubicin
KW - drug delivery
KW - peritoneal metastasis
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85107984687&partnerID=8YFLogxK
U2 - 10.1080/10717544.2021.1937382
DO - 10.1080/10717544.2021.1937382
M3 - Article
C2 - 34121568
AN - SCOPUS:85107984687
SN - 1071-7544
VL - 28
SP - 1179
EP - 1187
JO - Drug Delivery
JF - Drug Delivery
IS - 1
ER -