Electrostatic Intraperitoneal Aerosol Delivery of Nanoparticles: Proof of Concept and Preclinical Validation

Leen Van de Sande, Mohammad Rahimi-Gorji, Silvia Giordano, Enrico Davoli, Cristina Matteo, Sönke Detlefsen, Katharina D’Herde, Helena Braet, Molood Shariati, Katrien Remaut, Feifan Xie, Charlotte Debbaut, Ghader Ghorbaniasl, Sarah Cosyns, Wouter Willaert, Wim Ceelen

Research output: Contribution to journalArticle

Abstract

There is an increasing interest in intraperitoneal delivery of chemotherapy as an aerosol in patients with peritoneal metastasis. The currently used technology is hampered by inhomogenous drug delivery throughout the peritoneal cavity because of gravity, drag, and inertial impaction. Addition of an electrical force to aerosol particles, exerted by an electrostatic field, can improve spatial aerosol homogeneity and enhance tissue penetration. A computational fluid dynamics model shows that electrostatic precipitation (EP) results in a significantly improved aerosol distribution. Fluorescent nanoparticles (NPs) remain stable after nebulization in vitro, while EP significantly improves spatial homogeneity of NP distribution. Next, pressurized intraperitoneal chemotherapy with and without EP using NP albumin bound paclitaxel (Nab‐PTX) in a novel rat model is examined. EP does not worsen the effects of CO2 insufflation and intraperitoneal Nab‐PTX on mesothelial structural integrity or the severity of peritoneal inflammation. Importantly, EP significantly enhances tissue penetration of Nab‐PTX in the anatomical regions not facing the nozzle of the nebulizer. Also, the addition of EP leads to more homogenous peritoneal tissue concentrations of Nab‐PTX, in parallel with higher plasma concentrations. In conclusion, EP enhances spatial homogeneity and tissue uptake after intraperitoneal nebulization of anticancer NPs
Original languageEnglish
Number of pages11
JournalAdvanced Healthcare Materials
Volume9
Issue number16
DOIs
Publication statusPublished - 2020

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