Braet Helena, Andretto Valentina, Mariën Remco, Yücesan Beyza, van der Vegte Stefan, Haegebaert Ragna, Lollo Giovanna, De Smedt Stefaan C, Remaut Katrien
Department of Pharmaceutics, Ghent University, Ghent, Belgium; CRIG - Cancer Research Institute Ghent, Ghent, Belgium.
Laboratoire d'Automatique, de Génie des Procédés et de Génie Pharmaceutique (LAGEPP), Université Claude Bernard Lyon 1, Lyon, France.
Acta Biomater. 2023 Oct 15;170:318-329. doi: 10.1016/j.actbio.2023.08.027. Epub 2023 Aug 19.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is applied to treat unresectable peritoneal metastasis (PM), an advanced, end-stage disease with a poor prognosis. Electrostatic precipitation of the aerosol (ePIPAC) is aimed at improving the intraperitoneal (IP) drug distribution and tumor penetration. Also, the combination of nanoparticles (NPs) as drug delivery vehicles and IP aerosolization as administration method has been proposed as a promising tool to treat PM. There is currently limited knowledge on how electrostatic precipitation (ePIPAC) and high pressure nebulization (PIPAC) affects the performance of electrostatically formed complexes. Therefore, the stability, in vitro activity and ex vivo distribution and tissue penetration of negatively charged cisPt-pArg-HA NPs and positively charged siRNA-RNAiMAX NPs was evaluated following PIPAC and ePIPAC. Additionally, a multidirectional Medspray® nozzle was developed and compared with the currently used Capnopen® nozzle. For both NP types, PIPAC and ePIPAC did not negatively influence the in vitro activity, although limited aggregation of siRNA-RNAiMAX NPs was observed following nebulization with the Capnopen®. Importantly, ePIPAC was linked to a more uniform distribution and higher tissue penetration of the NPs aerosolized by both nozzles, independent on the NPs charge. Finally, compared to the Capnopen®, an increased NP deposition was observed at the top of the ex vivo model following aerosolization with the Medspray® nozzle, which indicates that this device possesses great potential for IP drug delivery purposes. STATEMENT OF SIGNIFICANCE: Aerosolized drug delivery in the peritoneal cavity holds great promise to treat peritoneal cancer. In addition, electrostatic precipitation of the aerosol to the peritoneal tissue is aimed at improving the drug distribution and tumor penetration. The combination of nanoparticles (NPs), which are nano-sized drug delivery vehicles, and aerosolization has been proposed as a promising tool to treat peritoneal cancer. However, there is currently limited knowledge on how electrostatic precipitation and aerosolization affect the performance of electrostatically formed NPs. Therefore, the stability, activity, distribution and penetration of negatively and positively charged NPs was evaluated after aerosolization and electrostatic precipitation. Additionally, to further optimize the local drug distribution, a multidirectional spray nozzle was developed and compared with the currently used nozzle.
腹腔内加压气雾化疗（PIPAC）用于治疗无法切除的腹膜转移（PM），这是一种预后不良的晚期终末期疾病。气雾的静电沉淀（ePIPAC）旨在改善腹腔内（IP）药物分布和肿瘤渗透。此外，已提出将纳米颗粒（NPs）作为药物递送载体与IP雾化作为给药方法相结合，作为治疗PM的一种有前景的工具。目前，关于静电沉淀（ePIPAC）和高压雾化（PIPAC）如何影响静电形成复合物的性能的知识有限。因此，在PIPAC和ePIPAC之后，评估了带负电荷的顺铂-聚精氨酸-透明质酸纳米颗粒（cisPt-pArg-HA NPs）和带正电荷的小干扰RNA-脂质体转染试剂（siRNA-RNAiMAX NPs）的稳定性、体外活性、离体分布和组织渗透。此外，还开发了一种多向Medspray®喷嘴，并与目前使用的Capnopen®喷嘴进行了比较。对于这两种类型的纳米颗粒，PIPAC和ePIPAC均未对体外活性产生负面影响，尽管在用Capnopen®雾化后观察到siRNA-RNAiMAX NPs有有限的聚集。重要的是，ePIPAC与两种喷嘴雾化的纳米颗粒更均匀的分布和更高的组织渗透有关，与纳米颗粒的电荷无关。最后，与Capnopen®相比，在用Medspray®喷嘴雾化后，在离体模型顶部观察到纳米颗粒沉积增加，这表明该装置在IP药物递送方面具有巨大潜力。重要性声明：腹腔内雾化药物递送在治疗腹膜癌方面具有很大前景。此外，将气雾静电沉淀到腹膜组织旨在改善药物分布和肿瘤渗透。已提出将纳米颗粒（NPs）（一种纳米尺寸的药物递送载体）与雾化相结合，作为治疗腹膜癌的一种有前景的工具。然而，目前关于静电沉淀和雾化如何影响静电形成的纳米颗粒性能的知识有限。因此，在雾化和静电沉淀后，评估了带负电荷和正电荷的纳米颗粒的稳定性、活性、分布和渗透。此外，为了进一步优化局部药物分布，开发了一种多向喷雾喷嘴，并与目前使用的喷嘴进行了比较。
