Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum.
Drug Deliv
; 28(1): 1179-1187, 2021 Dec.
Article
en En
| MEDLINE
| ID: mdl-34121568
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peritoneo
/
Doxorrubicina
/
Sistemas de Liberación de Medicamentos
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Antibióticos Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Drug Deliv
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2021
Tipo del documento:
Article