Comparative Analysis of PIPAC Nozzle Designs: Ex Vivo Evaluation of Aerosol Distribution, Penetration, and Tissue Concentration.

Abstract

A comparative ex vivo study was conducted to evaluate the impact of different nebulizer designs on spatial distribution, tissue concentration, and penetration depth of drugs delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC). Three nebulizer designs were evaluated in a PIPAC box: group 1 [full spray cone-multidirectional nebulizer (FSC-MDN)], group 2 [full spray cone-single directional nebulizer], and group 3 [hollow spray cone-single directional nebulizer]. Spatial aerosol deposition was measured using methylene blue for three-dimensional gravimetry in gram  (g). PIPACs with doxorubicin and cisplatin were performed to assess penetration depth (µm) and drug concentrations (µg/g) in porcine peritoneal tissue samples from the bottom, sides, and top of the box. Doxorubicin penetration was evaluated using fluorescence microscopy, and cisplatin concentrations were quantified using inductively coupled plasma mass spectrometry. Group 3 had significantly higher methylene blue deposition at the bottom (35.59 ± 1.46 g) compared with group 1 (24.2 ± 0.23 g, p = 0.0022) and group 2 (31.47 ± 0.52 g, p = 0.0001). Conversely, group 1 showed significantly greater side and top deposition (10.11 ± 0.26 g) than groups 2 (5.01 ± 0.68 g, p = 0.0022) and 3 (3.99 ± 0.42 g, p = 0.0022). Group 1 also demonstrated higher cisplatin concentrations (6.254 ± 2.57 µg/g, p = 0.05) and deeper doxorubicin penetration (179.9 ± 78.77 µm, p = 0.05) than the other groups. Compared with the other single directional nebulizers, group 1 (FSC-MDN) achieved greater side and top deposition, along with enhanced doxorubicin penetration and platinum concentration in the ex vivo PIPAC model.