加压腹膜内气溶胶化疗（PIPAC）是腹膜癌患者的一种新治疗方法。到目前为止，大多数已发表的研究都调查了通过 PIPAC 施用已确定的细胞抑制剂。本研究旨在评估 PIPAC 对两种突破性抗癌药物的效果，特别是抗 PD1 派姆单抗和抗 HER2 抗体药物偶联物 (ADC) - 曲妥珠单抗-deruxtecan。我们使用密封容器系统的实验装置，模拟腹腔并使用与临床使用相同的特征，对 PIPAC 给药前后临床相关浓度的派姆单抗和曲妥珠单抗-deruxtecan 样本进行了系统分析。我们利用一系列色谱和光谱技术来探索药物一级、二级和三级结构的潜在变化，重点关注雾化产生的翻译后修饰。我们的研究结果表明 PIPAC 并未损害所测试生物药品的完整性。通过尺寸排阻色谱 (SEC) 评估，两种药物的尺寸变异保持不变。反相液相色谱 (RPLC) 和疏水相互作用色谱 (HIC) 显示 PIPAC 治疗前后疏水性变异、平均药物抗体比 (DAR) 或 DAR 分布没有显着差异。圆二色性（CD）光谱证实二级和三级结构得以保留。虽然派姆单抗在 PIPAC 后显示电荷变体没有变化，但曲妥珠单抗-deruxtecan 在单克隆抗体本身的电荷变体数量上表现出不可忽略的变化，而有效负载保持不变。这种转变可能与 PIPAC 和这些实验中使用的 CapnoPen® 装置（由镍和铬制成）的金属成分有关。 总之，我们的结果表明 PIPAC 不会改变派姆单抗和曲妥珠单抗-deruxtecan 的结构，为未来的临床试验铺平道路。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan. We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of a hermetic container system, mimicking the abdominal cavity and using identical features as in clinical use. We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization. Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed-phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, the average drug-to-antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved. While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remained unchanged. This shift could possibly be related to the metallic composition of the CapnoPen® device (made of nickel and chromium) used in PIPAC and for these experiments. Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.