Samenvatting
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
Originele taal-2 | English |
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Aantal pagina's | 11 |
Tijdschrift | Advanced Healthcare Materials |
Volume | 9 |
Nummer van het tijdschrift | 16 |
DOI's | |
Status | Published - 2020 |
Bibliografische nota
Funding Information:L.V.d.S. and M.R.‐G. contributed equally to this work. The authors acknowledge the lab technicians Sabine De Groote and Silke Willekens for conduction of HE staining and the lab of pathology for conduction of MT staining. The authors also thank the Department of Morphology of the Faculty of Veterinary Medicine (Bart De Pauw) and the Centre for Microsystems Technology (CMST; Dieter Cuypers) of Ghent University for providing their scanning electron microscope. Margot Ceelen is thanked for providing Figure S2 in the Supporting Information. H.B. is a doctoral fellow from the Fund for Scientific Research Flanders (FWO‐SB). W.C. is a senior clinical researcher from the Fund for Scientific Research – Flanders (FWO). W.C. and K.R. are supported by a Concerted Research Action of Ghent University (G061119N). C.D. is supported by a postdoctoral fellowship from the Scientific Research Flanders (1202418N), and a starting grant from the special research fund of Ghent University (BOF/STA/201909/015).
Funding Information:
L.V.d.S. and M.R.-G. contributed equally to this work. The authors acknowledge the lab technicians Sabine De Groote and Silke Willekens for conduction of HE staining and the lab of pathology for conduction of MT staining. The authors also thank the Department of Morphology of the Faculty of Veterinary Medicine (Bart De Pauw) and the Centre for Microsystems Technology (CMST; Dieter Cuypers) of Ghent University for providing their scanning electron microscope. Margot Ceelen is thanked for providing Figure?S2 in the Supporting Information. H.B. is a doctoral fellow from the Fund for Scientific Research Flanders (FWO-SB). W.C. is a senior clinical researcher from the Fund for Scientific Research ? Flanders (FWO). W.C. and K.R. are supported by a Concerted Research Action of Ghent University (G061119N). C.D. is supported by a postdoctoral fellowship from the Scientific Research Flanders (1202418N), and a starting grant from the special research fund of Ghent University (BOF/STA/201909/015).
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