TY - JOUR
T1 - Electrostatic Intraperitoneal Aerosol Delivery of Nanoparticles
T2 - Proof of Concept and Preclinical Validation
AU - Van de Sande, Leen
AU - Rahimi-Gorji, Mohammad
AU - Giordano, Silvia
AU - Davoli, Enrico
AU - Matteo, Cristina
AU - Detlefsen, Sönke
AU - D'Herde, Katharina
AU - Braet, Helena
AU - Shariati, Molood
AU - Remaut, Katrien
AU - Xie, Feifan
AU - Debbaut, Charlotte
AU - Ghorbaniasl, Ghader
AU - Cosyns, Sarah
AU - Willaert, Wouter
AU - Ceelen, Wim
N1 - © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
U2 - 10.1002/adhm.202000655
DO - 10.1002/adhm.202000655
M3 - Journal article
C2 - 32548967
SN - 2192-2640
VL - 9
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 16
M1 - e2000655
ER -