Design and Validation of an Impaction-Nozzle Nebuliser for Enhanced Distribution Uniformity in Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC) Applications

用于增强加压腹腔内气溶胶化疗(PIPAC)应用中药物分布均匀性的撞击式喷嘴雾化器的设计与验证

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Abstract

INTRODUCTION: This study introduces and validates the CapnoTip(®), an impaction-based pressurised intraperitoneal aerosol chemotherapy (PIPAC) nebuliser designed to enhance intraperitoneal drug delivery and achieve greater homogeneity to improve treatment outcomes for peritoneal metastasis. METHODS: CapnoTip(®) was characterised through physical experiments evaluating aerosol granulometry, spray patterns, and aerosolisation angle. Pharmacological efficacy was assessed by using the ex vivo enhanced inverted bovine urinary bladder (eIBUB) model to measure intraperitoneal cisplatin concentration and distribution homogeneity and compare the result to that of the clinical reference nebuliser, CapnoPen(®). RESULTS: Aerosol granulometry using distilled water measured 26.1 µm (confidence interval [CI] 13.6-59.6) for CapnoTip(®) and 27.9 µm (CI 14.8-59.4) for CapnoPen(®). When using 10 cSt silicone oil, droplet sizes were 56.0 µm (CI 18.4-245.0) for CapnoTip(®) versus 33.8 µm (CI 14.3-66.5) for CapnoPen(®). The aerosolisation angle was broader with the CapnoTip(®) compared with the CapnoPen(®) (155.3° vs. 67.1°). CapnoTip(®) achieved a uniform intraperitoneal drug distribution, with no significant cisplatin gradient along the aerosolisation axis (p > 0.05). In contrast, CapnoPen(®) showed marked concentration gradients between the test organ's top vs. bottom and middle vs. bottom regions (p < 0.001). A significantly higher mean intraperitoneal cisplatin concentration was achieved with the CapnoTip(®) (56.8 ± 25.1 ng/mg) compared with the CapnoPen(®) (39.2 ± 31.1 ng/mg; p = 0.026). CONCLUSIONS: The CapnoTip(®) impaction-nozzle nebuliser for PIPAC is technically and pharmacologically equivalent to the CE-approved CapnoPen(®), while offering superior intraperitoneal drug delivery and distribution homogeneity.

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