Optimization of intraperitoneal aerosolized drug delivery using computational fluid dynamics (CFD) modeling

Mohammad Rahimi-Gorji, Charlotte Debbaut, Ghader Ghorbaniasl, Sarah Cosyns, Wouter Willaert, Wim Ceelen

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12 Citations (Scopus)
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Abstract

Intraperitoneal (IP) aerosolized anticancer drug delivery was recently introduced in the treatment of patients with peritoneal metastases. However, little is known on the effect of treatment parameters on the spatial distribution of the aerosol droplets in the peritoneal cavity. Here, computational fluid dynamics (CFD) modeling was used in conjunction with experimental validation in order to investigate the effect of droplet size, liquid flow rate and viscosity, and the addition of an electrostatic field on the homogeneity of IP aerosol. We found that spatial distribution is optimal with small droplet sizes (1–5 µm). Using the current clinically used technology (droplet size of 30 µm), the optimal spatial distribution of aerosol is obtained with a liquid flow rate of 0.6 mL/s. Compared to saline, nebulization of higher viscosity liquids results in less homogeneous aerosol distribution. The addition of electrostatic precipitation significantly improves homogeneity of aerosol distribution, but no further improvement is obtained with voltages higher than 6.5 kV. The results of the current study will allow to choose treatment parameters and settings in order to optimize spatial distribution of IP aerosolized drug, with a potential to enhance its anticancer effect.
Original languageEnglish
Article number6305
Number of pages16
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Apr 2022

Bibliographical note

Funding Information:
M.R-G. is supported by a grant from the special research fund of Ghent University (BOF). W.C. is a senior clinical investigator from the Fund for Scientific Research—Flanders (FWO). The authors thank Valérie Vanhoorne (Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University) for help with laser diffraction studies, Katrien Remaut and Helena Braet (Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University) for help with viscosity measurements, and Annelies Coene (Department of Electromechanical, Systems and Metal Engineering, Faculty of Engineering and Architecture, Ghent University) for support with high voltage applications. Also, the authors would like to acknowledge the support of the High-Performance Computing (HPC) center at Ghent University. The computational resources (Stevin Supercomputer Infrastructure) and services used for this work were provided by the VSC (Flemish Supercomputer Center), which is funded by Ghent University, the Fund for Scientific Research—Flanders (FWO), and the Flemish Government (Department of Economy, Science, and Innovation).

Funding Information:
M.R-G. is supported by a grant from the special research fund of Ghent University (BOF). W.C. is a senior clinical investigator from the Fund for Scientific Research?Flanders (FWO). The authors thank Val?rie Vanhoorne (Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University) for help with laser diffraction studies, Katrien Remaut and Helena Braet (Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University) for help with viscosity measurements, and Annelies Coene (Department of Electromechanical, Systems and Metal Engineering, Faculty of Engineering and Architecture, Ghent University) for support with high voltage applications. Also, the authors would like to acknowledge the support of the High-Performance Computing (HPC) center at Ghent University. The computational resources (Stevin Supercomputer Infrastructure) and services used for this work were provided by the VSC (Flemish Supercomputer Center), which is funded by Ghent University, the Fund for Scientific Research?Flanders (FWO), and the Flemish Government (Department of Economy, Science, and Innovation).

Publisher Copyright:
© 2022, The Author(s).

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

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