Comparative Evaluation of Nozzle Designs for Enhanced Oxaliplatin Delivery in Pressurized IntraPeritoneal Aerosol Chemotherapy: An In Vivo Study of a Porcine Model.

Abstract

Various nozzle designs are used in pressurized intraperitoneal aerosol chemotherapy (PIPAC), but comparative in vivo data on their pharmacologic effects are limited. Three groups of four pigs each received PIPAC with oxaliplatin (92 mg) using nebulizers with different designs: group 1 (full-spray-cone single directional), group 2 (hollow-spray-cone single directional), and group 3 (full-spray-cone multidirectional). Oxaliplatin concentrations (µg/g) were measured in blood, peritoneal tissue, and intra-abdominal fluid using inductively coupled plasma mass spectrometry. No significant differences in mean oxaliplatin concentrations in peritoneal tissue were observed: group 1 (12.37 ± 10.81 µg/g), group 2 (5.83 ± 6.18 µg/g), group 3 (9.46 ± 6.10 µg/g) ( p = 0.1002). However, group 3 had a significantly higher mean total oxaliplatin concentration in visceral peritoneal tissue (3.97 ± 0.63 µg/g) than group 1 (2.6 ± 0.56 µg/g) or group 2 (2.15 ± 0.37 µg/g ( p = 0.028). The mean total tissue uptake was also higher in group 3 (41.98 mg) than in group 1 (28.14 mg) or group 2 (36.65 mg) (p = 0.05). Pairwise comparisons showed no significant differences (group 1 vs group 2 [p = 0.1000], group 2 vs group 3 [p = 0.700]). No significant differences in blood absorption were noted (p = 0.106). The full-spray-cone multidirectional nebulizer design in group 3 resulted in significantly higher oxaliplatin concentrations in the small bowel peritoneum with greater total oxaliplatin tissue uptake than with the two other designs.